 |
 Previous Article | Next Article 
The Journal of Neuroscience, November 1, 1999, 19(21):9579-9586
A Single Exposure to Amphetamine Is Sufficient to Induce
Long-Term Behavioral, Neuroendocrine, and Neurochemical Sensitization
in Rats
Louk J. M. J.
Vanderschuren,
E.
Donné
Schmidt,
Taco J.
De Vries,
Caroline A. P.
Van Moorsel,
Fred J.H.
Tilders, and
Anton N. M.
Schoffelmeer
Research Institute Neurosciences Vrije Universiteit,
Department of Pharmacology, Medical Faculty, Free University, 1081 BT
Amsterdam, The Netherlands
 |
ABSTRACT |
Repeated treatment with psychostimulant drugs causes long-lasting
behavioral sensitization and associated neuroadaptations. Although
sensitization induced by a single psychostimulant exposure has also
been reported, information on the behavioral and neurochemical consequences of a single psychostimulant exposure is sparse. Therefore, to evaluate whether behavioral sensitization evoked by single and
repeated psychostimulant pretreatment regimens represent the same
neurobiological phenomenon, the time-dependent expression of
behavioral, neurochemical, and neuroendocrine sensitization after a
single exposure to amphetamine was investigated in rats. A single
exposure to amphetamine (5 mg/kg, i.p.) caused context-independent sensitization of the locomotor effects of amphetamine, which
intensified over time. Thus, sensitization to amphetamine was marginal
at 3 d after treatment and more evident after 1 week, whereas 3 weeks after treatment, profound sensitization, as well as
cross-sensitization, to cocaine was observed. Amphetamine pretreatment
caused an increase in the electrically evoked release of
[3H]dopamine from nucleus accumbens, caudate
putamen, and medial prefrontal cortex slices and of
[14C]acetylcholine from accumbens and caudate
slices. The hyperreactivity of dopaminergic nerve terminals appeared to
parallel the development of locomotor sensitization, i.e., whereas
hyperreactivity of accumbens dopaminergic terminals increased between
3 d and 3 weeks after treatment, the hyperreactivity of medial
prefrontal dopaminergic terminals decreased. Pre-exposure to
amphetamine also sensitized the hypothalamus-pituitary-adrenal axis
response to amphetamine at 1 and 3 weeks, but not at 3 d after
treatment. Because these data closely resemble those reported
previously for repeated amphetamine pretreatment, it is concluded that
a single exposure to amphetamine is sufficient to induce long-term
behavioral, neurochemical, and neuroendocrine sensitization in rats.
Key words:
amphetamine; locomotor sensitization; dopamine release; acetylcholine release; nucleus accumbens; hypothalamus-pituitary-adrenal axis; caudate putamen; medial
prefrontal cortex
| |
INTRODUCTION |
Repeated exposure to drugs of abuse
results in a progressive and enduring enhancement of their psychomotor
and positive reinforcing effects. This phenomenon, termed behavioral
sensitization (Stewart and Badiani, 1993 ), is thought to underlie
certain aspects of drug addiction and drug-induced psychosis (Robinson
and Becker, 1986; Robinson and Berridge, 1993; De Vries et al., 1998).
The expression of behavioral sensitization relies on time-dependent neuroplastic changes in the brain circuitry involved in motivational behavior. Of the numerous neuroadaptive phenomena involved,
long-lasting hyperreactivity of the mesolimbic dopaminergic pathway has
received most attention (for review, see Pierce and Kalivas, 1997).
The extent to which sensitization is induced by drug pre-exposure is
highly dependent on the nature of the pretreatment regimen. Thus,
repeated intermittent treatment with moderate doses of drugs is far
more effective in inducing sensitization than chronic exposure to high
or escalating drug doses (Post, 1980; Robinson and Becker, 1986;
Stewart and Badiani, 1993; Vanderschuren et al., 1997). Interestingly,
next to repeated intermittent and chronic administration schedules,
which both use multiple drug exposures, even a single exposure to
amphetamine or cocaine has been found to induce behavioral and
neurochemical sensitization (Robinson et al., 1982; Robinson, 1984;
Peris and Zahniser, 1987; Kalivas and Alesdatter, 1993). However, it is
not clear whether sensitization induced by single and repeated
psychostimulant exposure represents the same neurobiological phenomenon. For example, whereas there is a wealth of data on the
neuroadaptive consequences of repeated psychostimulant treatment (for
review, see White et al., 1995; Pierce and Kalivas, 1997; Wolf, 1998),
information on the neuroadaptive effects of a single psychostimulant
exposure is sparse (Robinson et al., 1982; Peris and Zahniser, 1987).
Furthermore, repeated psychostimulant treatment can induce behavioral
sensitization in both a context-dependent and a context-independent
manner (Stewart and Druhan, 1993; Anagnostaras and Robinson,
1996; Robinson et al., 1998; Vanderschuren et al., 1999a). However,
sensitization after a single drug pretreatment has only been
investigated in a context-dependent manner, meaning that tests for
sensitization were performed in the same environment in which
pretreatment took place, allowing for association of environmental cues
with drug effects. In view of the differences between context-dependent
and context-independent behavioral sensitization, both behaviorally
(Anagnostaras and Robinson, 1996; Robinson et al., 1998) and
neurobiologically (Hoffman and Wise, 1992; Li et al., 1997; Mead and
Stephens, 1998), it is of interest to investigate whether
context-independent sensitization also occurs after a single
psychostimulant exposure.
For these reasons, we evaluated the time-dependent behavioral,
neurochemical, and neuroendocrine effects of a single exposure to
amphetamine (5 mg/kg, IP) and compared them with the effects observed
previously after repeated amphetamine treatment. Thus, the time course
of amphetamine-induced context-independent sensitization to the
locomotor effects of amphetamine, as well as long-term cross-sensitization to cocaine and direct dopamine receptor agonists, was investigated. In addition, at various post-treatment intervals, we
investigated the effect of amphetamine pre-exposure on the electrically
evoked release of [3H]dopamine and
[14C]acetylcholine from slices of
nucleus accumbens, caudate putamen, and medial prefrontal cortex and on
the secretion of ACTH and corticosterone elicited by a challenge with amphetamine.
| |
MATERIALS AND METHODS |
Animals and amphetamine pretreatment. All experiments
were approved by the Animal Care Committee of the Free University of Amsterdam. Male Wistar rats (Harlan CPB, Zeist, The Netherlands), weighing 180-200 gm at the time of amphetamine or saline pretreatment, were housed two per cage in Macrolon cages under controlled
conditions (lights on from 7:00 A.M. to 7:00 P.M.). Animals were
allowed to accustom to the housing conditions for at least 1 week
before use. Food and water were available ad libitum.
Animals were briefly handled on the 2 d preceding pretreatment and
on the 2 d preceding subsequent drug challenges. Pretreatment
consisted of a single injection with amphetamine (5 mg/kg, i.p.) or
saline (1 ml/kg, i.p.), administered in the home cage. Amphetamine was
dissolved in sterile saline.
Determination of locomotor activity. Horizontal motor
activity was measured in perspex cages (40 × 40 × 35 cm)
using a video tracking system (EthoVision; Noldus Information
Technology B.V., Wageningen, The Netherlands), which determined the
position of the animal five times per second. Experiments were started
at approximately 9:30 A.M. White-noise was used to minimize the
influence of surrounding sounds. Locomotor challenge tests were
conducted as follows. Animals were allowed to habituate to the test
cages for 2 hr, during which activity was monitored. Then, animals
received an injection with saline (1.0 ml/kg, s.c. or i.p., depending
on the route of administration of the challenge drug), and activity was
monitored for 1 hr. Subsequently, animals were injected with amphetamine (1 mg/kg, i.p.), cocaine (15 mg/kg, i.p.), the dopamine D1
receptor agonist SKF-82958 (1 mg/kg, s.c.), the dopamine D2 receptor
agonist quinpirole (0.5 mg/kg, s.c.), or the nonselective dopamine
agonist apomorphine (0.3 mg/kg, s.c.). To examine the time course of
amphetamine sensitization, locomotor challenges with amphetamine were
performed 3 d, 1 week, or 3 weeks after treatment. To examine the
occurrence of long-term cross-sensitization to cocaine, SKF-82958,
quinpirole, and apomorphine, locomotor challenges with these drugs were
performed 3 weeks after treatment. The challenge doses of the drugs
represent the doses used previously to investigate dopaminergic
mechanisms involved in the expression of locomotor sensitization
induced by repeated amphetamine treatment (Vanderschuren et al.,
1999a). Animals were challenged only once. All drugs were dissolved in
sterile saline.
Determination of neurotransmitter release. Three days or 3 weeks after treatment, rats pre-exposed to saline or amphetamine were
decapitated, and nucleus accumbens, caudate putamen, and medial
prefrontal cortex were rapidly dissected. Tissue slices (0.3 × 0.3 × 1 mm) were prepared using a McIlwain tissue chopper and superfused as described previously (Schoffelmeer et al., 1994; Nestby et al., 1997). Slices (pooled tissue of two to three rats) were
washed twice with Krebs'-Ringer's bicarbonate medium containing (in
mM) 121 NaCl, 1.87 KCl, 1.17 KH2PO4, 1.17 MgSO4, 1.22 CaCl2, 25 NaHCO3, and 10 D-(+)-glucose, and subsequently incubated for 15 min in this medium under a constant atmosphere of 95%
O2-5% CO2 at 37°C.
After preincubation, the slices were rapidly washed and incubated for
15 min in 2.5 ml of medium containing 5 µCi [3H]dopamine and 2 µCi
[14C]choline, under an atmosphere of
95% O2-5% CO2 at 37°C.
Because the nucleus accumbens and medial prefrontal cortex have a dense noradrenergic innervation, 3 µM desipramine was
added during incubation to prevent accumulation of
[3H]dopamine in noradrenergic nerve
terminals. After labeling, the slices were rapidly washed and
transferred to each of 24 chambers of a superfusion apparatus (~4 mg
of tissue in 0.2 ml volume per chamber) and superfused (0.20 ml/min)
with medium gassed with 95% O2-5%
CO2 at 37°C.
In each experiment, neurotransmitter release from slices of saline- and
amphetamine-pretreated rats was studied simultaneously in 24 parallel
superfusion chambers. The superfusate was collected as 10 min samples
after 40 min of superfusion (t = 40 min).
Ca2+-dependent neurotransmitter release
was induced during superfusion by exposing the slices to electrical
biphasic block pulses (1 Hz, 30 mA, 2 msec pulses for nucleus accumbens
and caudate putamen slices; and 1 Hz, 15 mA, 2 msec pulses for medial
prefrontal cortex slices) for 10 min at t = 50 min
(electrical field stimulation).
The radioactivity remaining at the end of the experiment was extracted
from the tissue with 0.1 N HCl. The radioactivity in superfusion
fractions and tissue extracts was determined by liquid scintillation
counting. The efflux of radioactivity during each collection period was
expressed as a percentage of the amount of radioactivity in the slices
at the beginning of the respective collection period. The electrically
evoked release of neurotransmitter was calculated by subtracting the
spontaneous efflux of radioactivity from the total overflow of
radioactivity during stimulation and the next 10 min. A linear decline
from the 10 min interval before to that 20-30 min after the start of
stimulation was assumed for calculation of the spontaneous efflux of
radioactivity. The release evoked was expressed as percentage of the
content of radioactivity of the slices at the start of the stimulation period.
Determination of hypothalamus-pituitary-adrenal axis
activity. After a post-treatment interval of 3 d, 1 week, or
3 weeks, saline- or amphetamine-pretreated rats were injected with
amphetamine (1 mg/kg, i.p.), placed back into their home cages, and
decapitated 20 min later. Trunk blood was collected in ice-cold
heparin-coated tubes and centrifugated (1000 × g, 15 min, 4°C). Aliquots of plasma were stored at  20°C until assayed.
ACTH concentrations were measured as described previously (Van Oers et
al., 1992) using antiserum 8514 against the midportion of ACTH (Kovacs
and Makara, 1988). Synthetic rat ACTH was used as a standard. The
sensitivity of the assay was 10 pg/ml plasma (0.5 pg/tube). Plasma ACTH
concentrations were expressed as pg/ml plasma. Plasma corticosterone
levels were determined by radioimmunoassay (ICN Biochemicals, Costa
Mesa, CA) and expressed as nanograms per milliliter plasma. The
sensitivity of the assay was 0.7 ng/ml plasma.
Radiochemicals and drugs.
[3H]Dopamine (47 Ci/mmol) and
[14C]choline (15 mCi/mmol) were
purchased from the Radiochemical Center (Amersham Pharmacia Biotech,
Buckinghamshire, UK). ACTH was purchased from Peninsula Laboratories
(Belmont, CA). Desipramine, dopamine, and ()-sulpiride were purchased
from Sigma (St. Louis, MO). Morphine-HCl, (+)-amphetamine sulfate,
cocaine-HCl, and apomorphine-HCl were purchased from O.P.G.
(Utrecht, The Netherlands), (±)-SKF-82958-HBr and ()-quinpirole-HCl
were from Research Biochemicals (Natick, MA).
Statistics. Horizontal locomotor activity, expressed as
distance traveled (in centimeters) was calculated in 10 min blocks. Locomotor activity was analyzed using two-factor repeated-measures ANOVA for time block and pretreatment. Post hoc comparisons
were performed using Student-Newman-Keuls tests. In vitro
neurotransmitter release and plasma ACTH and corticosterone
concentrations were calculated as percentage of values from
saline-pretreated rats in the respective experiment. Observations of
different experiments were pooled and analyzed using one-way ANOVA.
| |
RESULTS |
Time-dependent locomotor sensitization to amphetamine
The locomotor effects of amphetamine (1 mg/kg, i.p.) in saline-
and amphetamine-pretreated rats after various post-treatment intervals
are presented in Figure
1A-C. The locomotor
effect of amphetamine was enhanced in rats pre-exposed to amphetamine
at 3 d, 1 week, and 3 weeks after treatment, but to a different
degree. Three days after exposure, the locomotor effects of amphetamine were only marginally affected by amphetamine pretreatment
(pretreatment, F(1,44) = 0.04; NS;
pretreatment × time, F(8,352) = 3.29; p < 0.01), sensitization being evident
during the second 10 min time block only (Fig. 1A).
One week after treatment, a more marked amphetamine pretreatment effect
was found (pretreatment, F(1,30) = 3.45; p = 0.07;) pretreatment × time,
F(8,240) = 3.82; p < 0.0001). In amphetamine-pre-exposed rats, the locomotor effects of
amphetamine were enhanced during the first three 10 min time blocks
(Fig. 1B). A clear-cut sensitization of the locomotor
effects of amphetamine in amphetamine-pre-exposed animals was observed
3 weeks after treatment (pretreatment,
F(1,27) = 11.48; p < 0.01; pretreatment × time,
F(8,216) = 2.58; p < 0.05). Post hoc analysis showed a significant enhancement of
amphetamine-induced hyperlocomotion during the first six 10 min time
blocks (Fig. 1C). Pretreatment with amphetamine did not
result in altered locomotion during the habituation phases (data not
shown) and the challenges with saline, irrespective of
the post-treatment interval at which testing was performed (Fig.
1A-C).
View larger version (19K):
[in this window]
[in a new window]
|
Figure 1.
Locomotor responses to amphetamine (1 mg/kg, i.p.)
in rats pretreated with amphetamine [AMPH; 1 × 5 mg/kg, i.p.; n = 22 (A);
n = 16 (B);
n = 14 (C); filled
circles] or saline [SAL; n = 24 (A); n = 16 (B); n = 15 (C); open circles] 3 d
(A), 1 week (B), or 3 weeks
(C) after treatment. After 2 hr habituation to
the test cages, the animals were injected with saline (1 ml/kg, i.p.)
and 1 hr later with amphetamine, after which activity was monitored for
1.5 hr. Data are expressed as mean ± SEM traveled distance (in
centimeters) per 10 min interval. *p < 0.05, different from saline-pretreated rats (Student-Newman-Keuls).
|
|
Long-term cross-sensitization to cocaine and dopamine
receptor agonists
The long-term effects of a single pre-exposure to 5 mg/kg
amphetamine on locomotor activity induced by cocaine and dopamine receptor agonists are presented in Figure
2. Three weeks after treatment,
amphetamine-pre-exposed rats were sensitized to the locomotor effects
of cocaine (15 mg/kg, i.p.) (pretreatment,
F(1,13) = 4.49; p = 0.05; pretreatment × time,
F(8,104) = 2.41; p < 0.05). Post hoc analysis revealed a significant enhancement
of the locomotor effect of cocaine during three 10 min time blocks
(Fig. 2A). In animals pretreated with amphetamine,
the locomotor effect of the D1 receptor agonist SKF-82958 was altered.
The overall locomotor effect of SKF-82958 appeared not to be
affected at all by amphetamine pretreatment (total distance
traveled, 14053 ± 2919 cm in saline-pre-exposed rats
and 13794 ± 3223 cm in amphetamine-pre-exposed rats;
pretreatment, F(1,30) = 0.00; NS).
However, the time course of SKF-82958 locomotion was altered in
amphetamine-pre-exposed animals (pretreatment × time,
F(14,420) = 3.48; p < 0.0001); post hoc tests revealed a significant increase in
the locomotor effect of SKF-82958 in amphetamine-pretreated rats during
the first two 10 min time blocks (Fig. 2B). When
saline- and amphetamine-pretreated rats were challenged with the D2
receptor agonist quinpirole, a tendency toward sensitization in
amphetamine-pretreated rats was found (pretreatment,
F(1,12) = 4.24; p = 0.06; pretreatment × time,
F(23,276) = 0.85; NS) (Fig.
2C). The locomotor effects of the nonselective dopamine
receptor agonist apomorphine did not differ between rats pretreated
with saline and amphetamine (pretreatment,
F(1,14) = 0.36; NS; pretreatment × time, F(8,112) = 1.81; NS) (Fig.
2D). Amphetamine pre-exposure did not result in
altered locomotion during the habituation phases (data not shown) and
the challenges with saline (Fig. 2A-D).
View larger version (19K):
[in this window]
[in a new window]
|
Figure 2.
Locomotor responses to cocaine (15 mg/kg,
i.p.; A), SKF-82958 (1 mg/kg, s.c.; B),
quinpirole (0.5 mg/kg, s.c.; C), or apomorphine (0.3 mg/kg, s.c.; D) in rats pretreated with amphetamine
[AMPH; 1 × 5 mg/kg, i.p.; n = 8 (A); n = 16 (B); n = 7 (C); n = 8 (D); filled
circles] or saline [SAL;
n = 7 (A);
n = 16 (B);
n = 7 (C);
n = 8 (D); open
circles] 3 weeks after treatment. After 2 hr habituation to
the test cages, the animals were injected with saline (1 ml/kg, s.c. or
i.p.) and 1 hr later with the challenge drug, after which activity was
monitored for 1.5-4 hr. Data are expressed as mean ± SEM
traveled distance (in centimeters) per 10 min interval.
*p < 0.05, different from saline-pretreated rats
(Student-Newman-Keuls).
|
|
Time-dependent adaptive changes in forebrain dopamine and
acetylcholine neurotransmission
Studying the electrically evoked release of
[3H]dopamine and
[14C]acetylcholine, the effect of
amphetamine pretreatment on the reactivity of dopaminergic and
cholinergic nerve terminals in nucleus accumbens, caudate putamen, and
medial prefrontal cortex toward depolarization was investigated 3 d and 3 weeks after treatment. In slices of saline-pretreated rats, the
electrically stimulated [3H]dopamine
release in excess of spontaneous [3H]
efflux in slices of nucleus accumbens, caudate putamen, and medial
prefrontal cortex amounted to 1.6 ± 0.1, 2.4 ± 0.2, and 3.8 ± 0.2% of total tissue radioactivity, respectively. The
electrically stimulated
[14C]acetylcholine release in excess of
spontaneous [14C] efflux in slices of
nucleus accumbens and caudate putamen, respectively, amounted to
4.2 ± 0.3 and 6.0 ± 0.4% of total tissue radioactivity.
Because the electrically evoked release of
[14C]acetylcholine from medial
prefrontal cortex slices hardly exceeded the spontaneous efflux of
radioactivity, [14C]acetylcholine
release data from medial prefrontal cortex slices are not presented.
As shown in Figure 3, the responsiveness
of all types of nerve terminals investigated was increased at both time
points as a consequence of amphetamine pretreatment. In nucleus
accumbens slices, the amphetamine-induced hyperreactivity of
dopaminergic nerve terminals increased over time (3 d vs 3 weeks,
F(1,76) = 4.41; p < 0.05), from a 41% increase 3 d
(F(1,63) = 12.35; p < 0.001) to a 69% increase 3 weeks
(F(1,83) = 39.31; p < 0.0001) after treatment. On the other hand, the responsiveness of
cholinergic nerve terminals in nucleus accumbens slices as a result of
pretreatment with amphetamine was enhanced to a similar degree at both
time points: 39% at 3 d (F(1,65) = 12.21; p < 0.001) and 41% at 3 weeks (F(1,85) = 32.64; p < 0.0001) after treatment (Fig. 3A). The neuroadaptive effects
of amphetamine-pretreatment observed in caudate putamen were comparable
but smaller than those found in the accumbens. The hyperresponsiveness
of dopaminergic nerve terminals increased, from an enhancement of 20%
at 3 d (F(1,58) = 6.97;
p < 0.05) to 34% at 3 weeks
(F(1,55) = 16.50; p < 0.001) after treatment, but this time effect was not significant (3 d
vs 3 weeks, F(1,56) = 2.11; NS).
Amphetamine-induced hyperreactivity of cholinergic nerve terminals in
caudate putamen slices was comparable at both time points: 37% at
3 d (F(1,55) = 16.82;
p < 0.001) and 34% at 3 weeks
(F(1,66) = 12.67; p < 0.001) after treatment (Fig. 3B). With regard to
hyperresponsiveness of dopaminergic nerve terminals in medial
prefrontal cortex slices, a picture opposite from that observed in
accumbens and caudate slices emerged. As a result of pre-exposure to
amphetamine, neuronal responsiveness was increased at 3 d after
treatment by 78% (F(1,30) = 38.14;
p < 0.0001), and this effect significantly declined (3 d vs 3 weeks, F(1,37) = 12.90;
p < 0.01) to a 36% increase at 3 weeks after
treatment (F(1,41) = 24.01;
p < 0.0001) (Fig. 3C).
View larger version (10K):
[in this window]
[in a new window]
|
Figure 3.
A, Enhancement of the electrically
evoked release of [3H]dopamine and
[14C]acetylcholine from superfused nucleus
accumbens slices of rats as a result of pre-exposure to amphetamine
(1 × 5 mg/kg, i.p.) 3 d (open bars) or 3 weeks (filled bars) after
treatment. B, Enhancement of the electrically evoked
release of [3H]dopamine and
[14C]acetylcholine from superfused caudate putamen
slices of rats as a result of pre-exposure to amphetamine (1 × 5 mg/kg, i.p.) 3 d (open bars) or 3 weeks
(filled bars) after treatment. C,
Enhancement of the electrically evoked release of
[3H]dopamine from superfused medial prefrontal
cortex slices of rats as a result of pre-exposure to amphetamine
(1 × 5 mg/kg, i.p.) 3 d (open bars) or 3 weeks (filled bars) after treatment. Data are
expressed as percent increase above electrically evoked release in
slices of saline-pretreated rats and represent means ± SEM of
15-45 observations. *p < 0.05;
**p < 0.001; ***p < 0.0001, different from saline pretreatment (ANOVA); +p < 0.05; ++p < 0.01, 3 d after treatment differs
from 3 weeks after treatment (ANOVA).
|
|
Time-dependent sensitization of the
hypothalamus-pituitary-adrenal axis
The effects of amphetamine (1 mg/kg, i.p.) on plasma
concentrations of ACTH and corticosterone in rats pretreated with
saline or amphetamine are presented in Figure
4, A and B,
respectively. There was a considerable variation between experiments
regarding the magnitude of neuroendocrine parameters determined. In
saline-pretreated rats, amphetamine-induced plasma concentrations of
ACTH varied between 51.7 ± 9.4 and 148.4 ± 11.0 pg/ml and
plasma corticosterone between 43.3 ± 5.4 and 121.2 ± 15.1 ng/ml. Despite this variation, there were clear-cut effects of
amphetamine pre-exposure on hypothalamus-pituitary-adrenal axis
reactivity to amphetamine. Three days after treatment, no effect of
amphetamine pre-exposure on the amphetamine-induced increase in the
secretion of ACTH (F(1,8) = 0.03; NS)
(Fig. 4A) and corticosterone
(F(1,8) = 0.21; NS) (Fig.
4B) was observed. One week after treatment, the
amphetamine-induced increase in both ACTH and corticosterone secretion
were significantly augmented in amphetamine-pretreated rats; the
secretion of ACTH was increased by 43%
(F(1,9) = 7.06; p < 0.05) (Fig. 4A) and the secretion of corticosterone
by 84% (F(1,8) = 8.31;
p < 0.05) (Fig. 4B). Comparable effects were observed at 3 weeks after treatment, i.e., in animals pretreated with amphetamine, amphetamine-induced ACTH concentrations were increased by 34% (F(1,9) = 5.50;
p < 0.05) (Fig. 4A) and corticosterone concentrations by 73%
(F(1,11) = 18.03; p < 0.01) (Fig. 4B).
View larger version (12K):
[in this window]
[in a new window]
|
Figure 4.
Plasma concentrations of ACTH
(A) and corticosterone (B)
induced by a challenge with amphetamine in rats pretreated with
amphetamine (AMPH; 1 × 5 mg/kg, i.p.;
filled bars) or saline (SAL; open
bars) 3 d, 1 week, or 3 weeks after treatment. Groups of
rats (n = 4-6) were injected with amphetamine (1 mg/kg, i.p.) in their home cages and decapitated 20 min later. Trunk
blood was collected, and plasma ACTH and corticosterone concentrations
were determined by radioimmunoassay. Results are presented as
percentage of plasma concentrations in saline-pretreated rats. Values
represent means ± SEM. *p < 0.05;
**p < 0.01, different from saline pretreatment
(ANOVA).
|
|
| |
DISCUSSION |
The main finding in the present study is that a single exposure to
amphetamine (5 mg/kg, i.p.) causes long-lasting behavioral sensitization associated with neurochemical and neuroendocrine adaptations. Amphetamine-induced behavioral sensitization was expressed
in a context-independent manner and gradually developed after
pretreatment, with sensitization being most pronounced at 3 weeks after
treatment. Moreover, a long-lasting cross-sensitization to cocaine and
a tendency toward cross-sensitization to the dopamine D2 receptor
agonist quinpirole was found after pre-exposure to amphetamine.
Amphetamine pretreatment caused a time-dependent hyperreactivity toward
depolarization of dopaminergic nerve terminals in the nucleus
accumbens, caudate putamen, and medial prefrontal cortex and
cholinergic nerve terminals in nucleus accumbens and caudate putamen.
In addition, a delayed hyperreactivity of the hypothalamus-pituitary-adrenal axis toward an amphetamine challenge was induced by amphetamine pretreatment. Together, the effects of a
single exposure to amphetamine closely resemble those we (Nestby et
al., 1997; Schmidt et al., 1999; Vanderschuren et al., 1999a,b) and
others (for review, see Pierce and Kalivas, 1997) have found previously
after repeated amphetamine pretreatment. We therefore conclude that a
single exposure to amphetamine is sufficient to induce long-lasting
behavioral, neurochemical, and neuroendocrine sensitization in rats.
Long-term behavioral sensitization evoked by a single psychostimulant
exposure has been reported previously, but the present study is the
first to show that this can occur in a context-independent manner,
meaning that pretreatment and challenge injections were administered in
separate environments. In this respect, it is important to note that
during neither habituation phases nor saline challenges locomotor
activity differed between amphetamine- and saline-pretreated rats. This
indicates that amphetamine pretreatment did not induce changes in basal
or novelty-induced locomotion or a conditioned psychomotor response to
the injection. Therefore, the observed locomotor sensitization most
likely represents a nonassociative increase in the sensitivity to the
locomotor effects of psychostimulant drugs, as a result of
neuroadaptive changes induced by amphetamine pretreatment.
With regard to locomotor sensitization, the pattern of effects evoked
by a single pre-exposure to amphetamine strikingly resembled that
induced by repeated amphetamine pretreatment. Thus, the magnitude of
amphetamine-induced sensitization to the locomotor effects of
amphetamine gradually increased with prolonged withdrawal (i.e., between 3 d and 3 weeks after treatment), which has also been observed after repeated amphetamine pretreatment (Kolta et al., 1985;
Paulson et al., 1991; Vanderschuren et al., 1999b). In addition, just
like repeated amphetamine pretreatment (Conway and Uretsky, 1982;
Robinson, 1984; Kalivas and Weber, 1988; Vanderschuren et al.,
1999a,b), single amphetamine caused cross-sensitization to cocaine but
not to morphine and apomorphine. Also, both regimens induced
cross-sensitization to quinpirole but to different degrees, i.e., a
robust sensitization after repeated amphetamine (Ujike et al., 1990;
Vanderschuren et al., 1999a), whereas cross-sensitization to quinpirole
after single amphetamine just failed to reach statistical significance.
There was a slight difference between single and repeated amphetamine
with regard to the onset of the locomotor response to SKF-82958, which
appeared to be somewhat faster after single amphetamine but slower
after repeated amphetamine (Vanderschuren et al., 1999a). The reason
for this discrepancy remains to be clarified.
Neuroadaptive changes in mesotelencephalic dopaminergic projections
play a prominent role in the induction and expression of amphetamine
sensitization. Whereas sensitization can be induced by microinjection
of amphetamine into the ventral tegmental area, the cell body region of
the mesolimbic dopaminergic system (Kalivas and Weber, 1988; Perugini
and Vezina, 1994; Cador et al., 1995), its expression is associated
with time-dependent adaptations in forebrain dopaminergic terminal
areas, such as the nucleus accumbens and caudate putamen (Kolta et al.,
1985; Robinson et al., 1988; Wolf et al., 1993; Paulson and Robinson,
1995). Dopaminergic neurotransmission in nucleus accumbens and caudate
putamen plays a critical role in the locomotor and stereotypic effects
of psychostimulant drugs, respectively (Kelly et al., 1975; Pijnenburg
et al., 1975; Sharp et al., 1987; Delfs et al., 1990). Therefore, it is
likely that hyperresponsiveness of striatal dopaminergic nerve
terminals plays a major role in the expression of psychostimulant
sensitization. Indeed, in particular, after extended post-treatment
intervals (>1 week), there appears to be a close correlation between
hyperreactivity of striatal dopaminergic neurotransmission and
expression of behavioral sensitization. On the other hand,
inconsistencies in the occurrence of these phenomena have been reported
after short post-treatment intervals (for review, see Pierce and
Kalivas, 1997). In the present study, a single amphetamine exposure
induced hyperreactivity toward electrical depolarization of
dopaminergic nerve terminals in the nucleus accumbens and caudate
putamen, an effect that increased between 3 d and 3 weeks after
treatment. This is consistent with findings reported after repeated
amphetamine pretreatment, using both in vitro and in
vivo preparations (Kolta et al., 1985; Wolf et al., 1993; Paulson
and Robinson, 1995; Nestby et al., 1997). We observed a strong
relationship between hyperreactivity of accumbens dopaminergic
neurotransmission and expression of locomotor sensitization to
amphetamine, in that both phenomena gradually intensified with prolonged withdrawal. On the other hand, at 3 d after treatment, accumbens dopaminergic nerve terminals were markedly hyperreactive, but
locomotor sensitization to amphetamine was only marginal. A possible
explanation for this could be that the expression of amphetamine
sensitization depends on the balance between dopamine neurotransmission
in the nucleus accumbens and medial prefrontal cortex. Thus, consistent
with the effects of repeated amphetamine pretreatment (Stephans and
Yamamoto, 1995; L. J. M. J. Vanderschuren, unpublished
observations), we found that a single exposure to amphetamine
resulted in an enduring hyperreactivity of medial prefrontal
dopaminergic nerve terminals. Remarkably, however, hyperreactivity of
medial prefrontal dopaminergic nerve terminals decreased with prolonged
withdrawal, displaying an opposite time course to the hyperreactivity
of accumbens dopaminergic terminals. Increased dopaminergic
neurotransmission in the medial prefrontal cortex is known to inhibit
accumbens dopaminergic neurotransmission, as well as
psychostimulant-induced locomotion (Louilot et al., 1989; Vezina et
al., 1991). It might therefore be that, especially after a short
post-treatment interval, hypersensitivity of medial prefrontal
dopaminergic terminals exerts an inhibitory influence on the expression
of amphetamine sensitization. Previous behavioral and neurochemical
studies (Banks and Gratton, 1995; Prasad et al., 1999) support such a
modulatory role of mesocortical dopaminergic neurotransmission in the
induction and expression of psychostimulant sensitization.
A single amphetamine exposure evoked enduring hyperreactivity of
cholinergic nerve terminals in nucleus accumbens and caudate putamen,
an effect that also occurred after repeated amphetamine pretreatment
(Nestby et al., 1997). Interestingly, an increase in striatal
acetylcholine release has been reported to correlate with the
expression of amphetamine sensitization (Bickerdike and Abercrombie,
1997). In addition, in striatal slices of morphine-sensitized rats,
enhanced cholinergic neurotransmission increased dopamine release
through activation of presynaptic muscarinic receptors (Schoffelmeer et
al., 1995). Because striatal dopamine release can be stimulated by
activation of presynaptic muscarinic (Schoffelmeer et al., 1995;
Smolders et al., 1997) and nicotinic (Rowell et al., 1987; Mifsud et
al., 1989; Marshall et al., 1997) receptors, hyperreactivity of
cholinergic neurons may contribute to the expression of behavioral
sensitization through a sustained stimulatory effect on striatal
dopaminergic neurotransmission. Furthermore, interactions between
dopaminergic and cholinergic input into efferent striatal neurons (Di
Chiara et al., 1994) could also contribute to the expression of
behavioral sensitization.
The neuroendocrine consequences of a single exposure to amphetamine
were also similar to those after repeated amphetamine, i.e., in
amphetamine-pretreated animals a hypersecretion of ACTH and
corticosterone was found after an amphetamine challenge 3 weeks but not
3 d after treatment (Schmidt et al., 1999; E. D. Schmidt,
unpublished observations). Long-lasting sensitization of the
ACTH and corticosterone response to amphetamine may be involved in the
autonomic and affective consequences of amphetamine exposure, but a
crucial role in the expression of psychostimulant sensitization has
been questioned (Badiani et al., 1995; Johnson et al., 1995; Prasad et
al., 1996; Schmidt et al., 1999). On the other hand, the glucocorticoid
receptor antagonist mifepristone (RU486) blocked the expression of
amphetamine sensitization (De Vries et al., 1996). Also, glucocorticoid
receptor activation enhances dopamine neurotransmission (Ronken et al.,
1994; Piazza et al., 1996; Schoffelmeer et al., 1997), whereas
corticosterone may augment the locomotor effects of psychostimulant
drugs (Cador et al., 1993; Marinelli et al., 1994, 1997; but see
Badiani et al., 1995). Therefore, a facilitatory role for central
corticosteroid receptors in the expression of amphetamine sensitization
cannot be excluded.
Together, the present data suggest that a single exposure to
amphetamine is sufficient to induce long-lasting sensitization at the
behavioral, neurochemical, and neuroendocrine levels. Repeated exposure
to drugs of abuse induces a complex pattern of time-dependent adaptations in a variety of transmitter systems and brain regions, ultimately resulting in long-lasting behavioral sensitization (for
review, see White et al., 1995; Pierce and Kalivas, 1997; Wolf, 1998).
It has been hypothesized that this cascade of neuroadaptations is
driven by phasic alterations in gene expression. Mechanistic similarities between behavioral sensitization and other forms of
neuronal plasticity, such as long-term memory, have been suggested. For
instance, just like long-term memory (Tully, 1998), the induction of
long-lasting behavioral sensitization requires novel protein synthesis
(Karler et al., 1993; Shimosato and Saito, 1993; Sorg and Ulibarri,
1995), structural changes at relevant synapses (Robinson and Kolb,
1997), and is most effectively induced by intermittent stimulation
(Post, 1980; Robinson and Becker, 1986; Stewart and Badiani, 1993;
Vanderschuren et al., 1997). The present study adds another similarity
between long-term memory and long-lasting behavioral sensitization, in
that both phenomena and their associated neuroadaptations can be
induced by a single pertinent stimulus.
| |
FOOTNOTES |
Received June 23, 1999; revised Aug. 11, 1999; accepted Aug. 12, 1999.
This work was supported by Netherlands Organization for Scientific
Research (NWO) Grants 903-42-007 and 900-43-128.
Correspondence should be addressed to Dr. Louk J. M. J. Vanderschuren,
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der
Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
| |
REFERENCES |
-
Anagnostaras SG,
Robinson TE
(1996)
Senzitization to the psychomotor stimulant effects of amphetamine: modulation by associative learning.
Behav Neurosci
110:1397-1414[Web of Science][Medline].
-
Badiani A,
Morano MI,
Akil H,
Robinson TE
(1995)
Circulating adrenal hormones are not necessary for the development of sensitization to the psychomotor activating effects of amphetamine.
Brain Res
673:13-24[Web of Science][Medline].
-
Banks KE,
Gratton A
(1995)
Possible involvement of medial prefrontal cortex in amphetamine-induced sensitization of mesolimbic dopamine function.
Eur J Pharmacol
282:157-167[Web of Science][Medline].
-
Bickerdike MJ,
Abercrombie ED
(1997)
Striatal acetylcholine release correlates with behavioral sensitization in rats withdrawn from chronic amphetamine.
J Pharmacol Exp Ther
282:818-826[Abstract/Free Full Text].
-
Cador M,
Dulluc J,
Mormède P
(1993)
Modulation of the locomotor response to amphetamine by corticosterone.
Neuroscience
56:981-988[Web of Science][Medline].
-
Cador M,
Bjijou Y,
Stinus L
(1995)
Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine.
Neuroscience
65:385-395[Web of Science][Medline].
-
Conway PG,
Uretsky NJ
(1982)
Role of striatal dopaminergic receptors in amphetamine-induced behavioral facilitation.
J Pharmacol Exp Ther
221:650-655[Free Full Text].
-
De Vries TJ,
Schoffelmeer ANM,
Tjon GHK,
Nestby P,
Mulder AH,
Vanderschuren LJMJ
(1996)
Mifepristone prevents the expression of behavioural sensitization to amphetamine.
Eur J Pharmacol
307:R3-R4[Medline].
-
De Vries TJ,
Schoffelmeer ANM,
Binnekade R,
Mulder AH,
Vanderschuren LJMJ
(1998)
Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization.
Eur J Neurosci
10:3565-3571[Web of Science][Medline].
-
Delfs JM,
Schreiber L,
Kelley AE
(1990)
Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat.
J Neurosci
10:303-310[Abstract].
-
Di Chiara G,
Morelli M,
Consolo S
(1994)
Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions.
Trends Neurosci
17:228-233[Web of Science][Medline].
-
Hoffman DC,
Wise RA
(1992)
Locomotor-activating effects of the D2 agonist bromocriptine show environment-specific sensitization following repeated injections.
Psychopharmacology
107:277-284[Medline].
-
Johnson DH,
Svensson AI,
Engel JA,
Söderpalm B
(1995)
Induction but not expression of behavioural sensitization to nicotine in the rat is dependent on glucocorticoids.
Eur J Pharmacol
276:155-164[Web of Science][Medline].
-
Kalivas PW,
Alesdatter JE
(1993)
Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine.
J Pharmacol Exp Ther
267:486-495[Abstract/Free Full Text].
-
Kalivas PW,
Weber B
(1988)
Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine.
J Pharmacol Exp Ther
245:1095-1102[Abstract/Free Full Text].
-
Karler R,
Finnegan KT,
Calder LD
(1993)
Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis.
Brain Res
603:19-24[Web of Science][Medline].
-
Kelly PH,
Seviour PW,
Iversen SD
(1975)
Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum.
Brain Res
94:507-522[Web of Science][Medline].
-
Kolta MG,
Shreve P,
De Souza V,
Uretsky NJ
(1985)
Time course of the development of the enhanced behavioral and biochemical responses to amphetamine after pretreatment with amphetamine.
Neuropharmacology
24:823-829[Web of Science][Medline].
-
Kovacs KJ,
Makara GB
(1988)
Corticosterone and dexamethasone act at different brain sites to inhibit adrenalectomy-induced adrenocorticotropin hypersecretion.
Brain Res
474:205-210[Web of Science][Medline].
-
Li Y,
Vartanian AJ,
White FJ,
Xue C-J,
Wolf ME
(1997)
Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine.
Psychopharmacology
134:266-276[Medline].
-
Louilot A,
Le Moal M,
Simon H
(1989)
Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study.
Neuroscience
29:45-56[Medline].
-
Marinelli M,
Piazza PV,
Deroche V,
Maccari S,
Le Moal M,
Simon H
(1994)
Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine.
J Neurosci
14:2724-2731[Abstract].
-
Marinelli M,
Rougé-Pont F,
Deroche V,
Barrot M,
De Jesus Oliveira C,
Le Moal M,
Piazza PV
(1997)
Glucocorticoids and behavioral effects of psychostimulants. I. Locomotor response to cocaine depends on basal levels of glucocorticoids.
J Pharmacol Exp Ther
281:1392-1400[Abstract/Free Full Text].
-
Marshall DL,
Redfern PH,
Wonnacott S
(1997)
Presynaptic nicotinic modulation of dopamine release in the three ascending pathways studied by in vivo microdialysis: comparison of naive and chronic nicotine-treated rats.
J Neurochem
68:1511-1519[Web of Science][Medline].
-
Mead AN,
Stephens DN
(1998)
AMPA-receptors are involved in the expression of amphetamine-induced behavioural sensitisation, but not in the expression of amphetamine-induced conditioned activity in mice.
Neuropharmacology
37:1131-1138[Medline].
-
Mifsud J-C,
Hernandez L,
Hoebel BG
(1989)
Nicotine infused into the nucleus accumbens increases synaptic dopamine as measured by in vivo microdialysis.
Brain Res
478:365-367[Web of Science][Medline].
-
Nestby P,
Vanderschuren LJMJ,
De Vries TJ,
Hogenboom F,
Wardeh G,
Mulder AH,
Schoffelmeer ANM
(1997)
Ethanol, like psychostimulants and morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: possible role in behavioural sensitization.
Psychopharmacology
133:69-76[Medline].
-
Paulson PE,
Robinson TE
(1995)
Amphetamine-induced time-dependent sensitization of dopamine-neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats.
Synapse
19:56-65[Web of Science][Medline].
-
Paulson PE,
Camp DM,
Robinson TE
(1991)
Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats.
Psychopharmacology
103:480-492[Medline].
-
Peris J,
Zahniser NR
(1987)
One injection of cocaine produces a long-lasting increase in [3H]-dopamine release.
Pharmacol Biochem Behav
27:533-535[Medline].
-
Perugini M,
Vezina P
(1994)
Amphetamine administered to the ventral tegmental area sensitizes rats to the locomotor effects of nucleus accumbens amphetamine.
J Pharmacol Exp Ther
270:690-696[Abstract/Free Full Text].
-
Piazza PV,
Rougé-Pont F,
Deroche V,
Maccari S,
Simon H,
Le Moal M
(1996)
Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.
Proc Natl Acad Sci USA
93:8716-8720[Abstract/Free Full Text].
-
Pierce RC,
Kalivas PW
(1997)
A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants.
Brain Res Rev
25:192-216[Medline].
-
Pijnenburg AJJ,
Honig WMM,
Van Rossum JM
(1975)
Inhibition of D-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat.
Psychopharmacologia
41:87-95.
-
Post RM
(1980)
Intermittent versus continuous stimulation: effect of time interval on the development of sensitization or tolerance.
Life Sci
26:1275-1282[Web of Science][Medline].
-
Prasad BM,
Ulibarri C,
Kalivas PW,
Sorg BA
(1996)
Effect of adrenalectomy on the initiation and expression of cocaine-induced sensitization.
Psychopharmacology
125:265-273[Medline].
-
Prasad BM,
Hochstatter T,
Sorg BA
(1999)
Expression of cocaine sensitization: regulation by the medial prefrontal cortex.
Neuroscience
88:765-774[Web of Science][Medline].
-
Robinson TE
(1984)
Behavioral sensitization: characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female rats.
Psychopharmacology
84:466-475[Medline].
-
Robinson TE,
Becker JB
(1986)
Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis.
Brain Res Rev
11:157-198.
-
Robinson TE,
Berridge KC
(1993)
The neural basis of drug craving: an incentive-sensitization theory of addiction.
Brain Res Rev
18:247-291[Medline].
-
Robinson TE,
Kolb B
(1997)
Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine.
J Neurosci
17:8491-8497[Abstract/Free Full Text].
-
Robinson TE,
Becker JB,
Presty SK
(1982)
Long-term facilitation of amphetamine-induced rotational behavior and striatal dopamine release produced by a single exposure to amphetamine: sex differences.
Brain Res
253:231-241[Web of Science][Medline].
-
Robinson TE,
Jurson PA,
Bennett JA,
Bentgen KM
(1988)
Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by previous experience with (+)-amphetamine: a microdialysis study in freely moving rats.
Brain Res
462:211-222[Web of Science][Medline].
-
Robinson TE,
Browman KE,
Crombag HS,
Badiani A
(1998)
Modulation of the induction or expression of psychostimulant sensitization by the circumstances surrounding drug administration.
Neurosci Biobehav Rev
22:347-354[Web of Science][Medline].
-
Ronken E,
Mulder AH,
Schoffelmeer ANM
(1994)
Glucocorticoid and mineralocorticoid receptors differentially modulate cultured dopaminergic neurons of rat ventral mesencephalon.
Eur J Pharmacol
263:149-156[Medline].
-
Rowell PP,
Carr LA,
Garner AC
(1987)
Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens.
J Neurochem
49:1449-1454[Web of Science][Medline].
-
Schmidt ED,
Tilders FJH,
Binnekade R,
Schoffelmeer ANM,
De Vries TJ
(1999)
Stressor- or drug-induced sensitization of the corticosterone response is not critically involved in the long-term expression of behavioral sensitization to amphetamine.
Neuroscience
92:343-352[Medline].
-
Schoffelmeer ANM,
Hogenboom F,
Mulder AH,
Ronken E,
Stoof JC,
Drukarch B
(1994)
Dopamine displays an identical apparent affinity towards functional dopamine D1 and D2 receptors in rat striatal slices: possible implications for the regulatory role of D2 receptors.
Synapse
17:190-195[Web of Science][Medline].
-
Schoffelmeer ANM,
Nestby P,
Tjon GHK,
Wardeh G,
De Vries TJ,
Vanderschuren LJMJ,
Mulder AH
(1995)
Intermittent morphine treatment causes a protracted increase in cholinergic striatal neurotransmission measured ex vivo.
Eur J Pharmacol
286:311-314[Medline].
-
Schoffelmeer ANM,
De Vries TJ,
Vanderschuren LJMJ,
Tjon GHK,
Nestby P,
Wardeh G,
Mulder AH
(1997)
Intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on dopamine D1 receptor functioning in rats striatal GABA neurons.
Synapse
25:381-388[Web of Science][Medline].
-
Sharp T,
Zetterström T,
Ljungberg T,
Ungerstedt U
(1987)
A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral microdialysis.
Brain Res
401:322-330[Web of Science][Medline].
-
Shimosato K,
Saito T
(1993)
Suppressive effect of cycloheximide on behavioral sensitization to methamphetamine in mice.
Eur J Pharmacol
234:67-75[Medline].
-
Smolders I,
Bogaert L,
Ebinger G,
Michotte Y
(1997)
Muscarinic modulation of striatal dopamine, glutamate, and GABA release, as measured with in vivo microdialysis.
J Neurochem
68:1942-1948[Web of Science][Medline].
-
Sorg BA,
Ulibarri C
(1995)
Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine.
Synapse
20:217-224[Web of Science][Medline].
-
Stephans SE,
Yamamoto BK
(1995)
Effect of repeated methamphetamine administrations on dopamine and glutamate efflux in rat prefrontal cortex.
Brain Res
700:99-106[Web of Science][Medline].
-
Stewart J,
Badiani A
(1993)
Tolerance and sensitization to the behavioral effects of drugs.
Behav Pharmacol
4:289-312[Web of Science][Medline].
-
Stewart J,
Druhan JP
(1993)
Development of both conditioning and sensitization of the behavioral activating effects of amphetamine is blocked by the non-competitive NMDA receptor antagonist, MK-801.
Psychopharmacology
110:125-132[Medline].
-
Tully T
(1998)
Toward a molecular biology of memory: the light's coming on!
Nature Neurosci
1:543-545.[Web of Science][Medline]
-
Ujike H,
Akiyama K,
Otsuki S
(1990)
D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine.
Psychopharmacology
102:459-464[Medline].
-
Van Oers JWAM,
Hinson JP,
Binnekade R,
Tilders FJH
(1992)
Physiological role of corticotropin-releasing factor in the control of adrenocorticotropin-mediated corticosterone release from the rat adrenal gland.
Endocrinology
130:282-288[Abstract/Free Full Text].
-
Vanderschuren LJMJ,
Tjon GHK,
Nestby P,
Mulder AH,
Schoffelmeer ANM,
De Vries TJ
(1997)
Morphine-induced long term sensitization to the locomotor effects of morphine and amphetamine depends on the temporal pattern of the pretreatment regimen.
Psychopharmacology
131:115-122[Medline].
-
Vanderschuren LJMJ,
Schoffelmeer ANM,
Mulder AH,
De Vries TJ
(1999a)
Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine.
Psychopharmacology
143:244-253[Medline].
-
Vanderschuren LJMJ,
Schoffelmeer ANM,
Mulder AH,
De Vries TJ
(1999b)
Lack of cross-sensitization of the locomotor effects of morphine in amphetamine-treated rats.
Neuropsychopharmacology
21:550-559[Medline].
-
Vezina P,
Blanc G,
Glowinski J,
Tassin JP
(1991)
Opposed behavioural outputs of increased dopamine transmission in prefrontocortical and subcortical areas: a role for the cortical D-1 dopamine receptor.
Eur J Neurosci
3:1001-1007[Web of Science][Medline].
-
White FJ,
Hu X-T,
Henry DJ,
Zhang X-F
(1995)
Neurophysiological alterations in the mesocorticolimbic dopamine system with repeated cocaine administration.
In: The neurobiology of cocaine (Hammer Jr RP,
ed), pp 99-119. Boca Raton, FL: CRC.
-
Wolf ME
(1998)
The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants.
Prog Neurobiol
54:679-720[Web of Science][Medline].
-
Wolf ME,
White FJ,
Nassar R,
Brooderson RJ,
Khansa MR
(1993)
Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization.
J Pharmacol Exp Ther
264:249-255[Abstract/Free Full Text].
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219579-08$05.00/0
This article has been cited by other articles:
|
|
|
|
 
M. A. Smith, J. L. Greene-Naples, J. N. Felder, J. C. Iordanou, M. A. Lyle, and K. L. Walker
The Effects of Repeated Opioid Administration on Locomotor Activity: II. Unidirectional Cross-Sensitization to Cocaine
J. Pharmacol. Exp. Ther.,
August 1, 2009;
330(2):
476 - 486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Pastor, C. S. McKinnon, A. C. Scibelli, S. Burkhart-Kasch, C. Reed, A. E. Ryabinin, S. C. Coste, M. P. Stenzel-Poore, and T. J. Phillips
From the Cover: Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin1-independent mechanism
PNAS,
July 1, 2008;
105(26):
9070 - 9075.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Jutkiewicz, M. G. Baladi, J. E. Folk, K. C. Rice, and J. H. Woods
The {delta}-Opioid Receptor Agonist SNC80 [(+)-4-[{alpha}(R)-{alpha}-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] Synergistically Enhances the Locomotor-Activating Effects of Some Psychomotor Stimulants, but Not Direct Dopamine Agonists, in Rats
J. Pharmacol. Exp. Ther.,
February 1, 2008;
324(2):
714 - 724.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. McBride and F. W. Flynn
Centrally administered vasopressin cross-sensitizes rats to amphetamine and drinking hypertonic NaCl
Am J Physiol Regulatory Integrative Comp Physiol,
September 1, 2007;
293(3):
R1452 - R1458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-G. Corbille, E. Valjent, G. Marsicano, C. Ledent, B. Lutz, D. Herve, and J.-A. Girault
Role of Cannabinoid Type 1 Receptors in Locomotor Activity and Striatal Signaling in Response to Psychostimulants
J. Neurosci.,
June 27, 2007;
27(26):
6937 - 6947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Boileau, A. Dagher, M. Leyton, R. N. Gunn, G. B. Baker, M. Diksic, and C. Benkelfat
Modeling Sensitization to Stimulants in Humans: An [11C]Raclopride/Positron Emission Tomography Study in Healthy Men
Arch Gen Psychiatry,
December 1, 2006;
63(12):
1386 - 1395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Valjent, A.-G. Corbille, J. Bertran-Gonzalez, D. Herve, and J.-A. Girault
Inhibition of ERK pathway or protein synthesis during reexposure to drugs of abuse erases previously learned place preference
PNAS,
February 21, 2006;
103(8):
2932 - 2937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Valjent, V. Pascoli, P. Svenningsson, S. Paul, H. Enslen, J.-C. Corvol, A. Stipanovich, J. Caboche, P. J. Lombroso, A. C. Nairn, et al.
From The Cover: Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum
PNAS,
January 11, 2005;
102(2):
491 - 496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Nitsche, J. Grundey, D. Liebetanz, N. Lang, F. Tergau, and W. Paulus
Catecholaminergic Consolidation of Motor Cortical Neuroplasticity in Humans
Cereb Cortex,
November 1, 2004;
14(11):
1240 - 1245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Kim, K. A. Pollak, G. O. Hjelmstad, and H. L. Fields
A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism
PNAS,
April 13, 2004;
101(15):
5664 - 5669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pierucci, V. Di Matteo, and E. Esposito
Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration
J. Pharmacol. Exp. Ther.,
April 1, 2004;
309(1):
109 - 118.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. Weinshenker, N. S. Miller, K. Blizinsky, M. L. Laughlin, and R. D. Palmiter
Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals
PNAS,
October 15, 2002;
99(21):
13873 - 13877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Glickstein, P. R. Hof, and C. Schmauss
Mice Lacking Dopamine D2 and D3 Receptors Have Spatial Working Memory Deficits
J. Neurosci.,
July 1, 2002;
22(13):
5619 - 5629.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Abarca, U. Albrecht, and R. Spanagel
Cocaine sensitization and reward are under the influence of circadian genes and rhythm
PNAS,
June 25, 2002;
99(13):
9026 - 9030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. M. Schoffelmeer, T. J. De Vries, G. Wardeh, H. W. M. van de Ven, and L. J. M. J. Vanderschuren
Psychostimulant-Induced Behavioral Sensitization Depends on Nicotinic Receptor Activation
J. Neurosci.,
April 15, 2002;
22(8):
3269 - 3276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nikaido, M. Akiyama, T. Moriya, and S. Shibata
Sensitized Increase of Period Gene Expression in the Mouse Caudate/Putamen Caused by Repeated Injection of Methamphetamine
Mol. Pharmacol.,
April 1, 2001;
59(4):
894 - 900.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
The Neuroscientist Comments
Neuroscientist,
June 1, 2000;
6(3):
139 - 142.
[PDF]
|
|
|
|
|
|
|
C. Schmauss
A Single Dose of Methamphetamine Leads to a Long Term Reversal of the Blunted Dopamine D1 Receptor-mediated Neocortical c-fos Responses in Mice Deficient for D2 and D3 Receptors
J. Biol. Chem.,
December 1, 2000;
275(49):
38944 - 38948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yang, C. K. Hwang, E. Junn, G. Lee, and M. M. Mouradian
ZIC2 and Sp3 Repress Sp1-induced Activation of the Human D1ADopamine Receptor Gene
J. Biol. Chem.,
December 1, 2000;
275(49):
38863 - 38869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
