 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, May 1, 2000, 20(9):3504-3511
Dual Effects of D-Amphetamine on Dopamine Neurons Mediated by Dopamine and Nondopamine Receptors
Wei-Xing Shi, Chen-Lun Pun, Xue-Xiang Zhang, Michelle D. Jones, and Benjamin S. Bunney Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
By increasing dopamine (DA) release and activating feedback mechanisms, amphetamine and related psychostimulants are known to inhibit DA cell firing. Here, we report that D-amphetamine also has an excitatory effect on DA cells, which under control conditions, is masked by the inhibitory effect of D-amphetamine and is revealed when D2-like receptors are blocked. Thus, using in vivo single-unit recording in rats, we found that the selective D2 antagonist raclopride not only blocked the inhibition induced by D-amphetamine but also enabled D-amphetamine to excite DA cells. The excitation, expressed as an increase in both firing rate and bursting, persisted when both D1- and D2-like receptors were blocked by SCH23390 and eticlopride, suggesting that it is not mediated by DA receptors. The norepinephrine uptake blocker nisoxetine mimicked the effect of D-amphetamine, especially the increase in bursting, whereas the 5-HT uptake blocker fluoxetine produced no significant effect. Adrenergic
1 antagonists prazosin and WB4101 and the nonselective
antagonist propranolole, however, failed to prevent D-amphetamine from producing the excitation. Thus, revising the traditional concept, this study suggests that D-amphetamine has two effects on DA cells, a DA-mediated inhibition and a non-DA-mediated excitation. The latter is mediated in part through adrenergic
Key words: amphetamine; drug abuse; addiction; psychostimulant; dopamine; norepinephrine; prazosin; adrenergic;
INTRODUCTION
Amphetamine and related psychostimulants, including cocaine, are known to block dopamine (DA) re-uptake and to increase DA release. Because of activation of DA autoreceptors and long-loop feedback pathways from DA-innervated areas, these drugs also inhibit DA cell firing (Bunney et al., 1973
; Einhorn et al., 1988
In the course of characterizing D-amphetamine-induced inhibition of DA neurons, we found that the selective D2 antagonist raclopride, injected after D-amphetamine, not only reversed the inhibition induced by D-amphetamine but further increased the activity of the cell to above baseline. Initially, this increase was thought to be a "rebound" phenomenon of the cell or to be attributable to blockade of a tonic DA inhibition induced by spontaneous DA release. When analyzing burst activity, we noticed that the level of bursting of the cell was increased several fold after raclopride. This large increase led us to suspect that mechanisms other than the two proposed above may be involved. In this report, we present evidence suggesting that D-amphetamine has, in addition to its well known inhibitory effect, an excitatory effect on DA cells. Under control conditions, this excitatory effect is masked by the inhibitory effect of D-amphetamine. Raclopride, by blocking the inhibitory effect, reveals the excitatory effect of D-amphetamine.
Parts of this work have been published previously in abstract form (Shi et al., 1997a
MATERIALS AND METHODS
Single-unit recordings in vivo. All procedures were performed in accordance with those outlined in the Guide for the Care and Use of Animals U.S. Government Principles, with Public Health Service Policy and the Animal Welfare Act, and approved by the Yale Animal Care and Use Committee. Male Sprague Dawley rats weighing between 250 and 400 gm were used. Most experiments were performed in chloral hydrate-anesthetized rats (400 mg/kg, i.p., with supplemental doses administered via a lateral tail vein). A few experiments were performed in nonanesthetized rats (low cerveau isolé preparations), which were prepared as described previously (Shi et al., 1997b
DA cells in the substantia nigra (SN) and ventral tegmental area (VTA) were identified and recorded extracellularly as described previously (Bunney et al., 1973
. The electrode was lowered through a small burr hole drilled above the SN and the VTA (3.0 mm anterior to the lamboidal suture and 0.5-2.5 mm lateral to the midline) using a hydraulic microdrive. DA cells were normally found between 6.5 and 8.5 mm below the cortical surface. Interspike intervals (ISI) and firing rates were collected on-line via an interface (Lab-PC+; National Instrument, Austin, Taxes) to a personal computer (DECpc 450ST) using software written in LabView for Windows (National Instrument, Austin, TX). The number of bursts, the total number of spikes in bursts, and variation coefficient of ISI were calculated every 10 sec using Visual Basic macros. The onset of a burst was identified as the concurrence of two spikes with an ISI <80 msec, and the termination of a burst was defined as an ISI >160 msec (Grace and Bunney, 1984
Drugs. All drugs were administered intravenously through a lateral tail vein. Doses were given as salts. Prazosin and phenoxybenzamine were dissolved in 25-30% polyethylene glycol (PEG) (average molecular weight of 200 kDa) at 2.5 mg/ml and 30 mg/ml, respectively. Immediately before injection, the solution was diluted with distilled water so that the final volume of injection was either 0.05 or 0.1 ml. Depending on the weight of the animal, the final concentration of PEG ranged from 4.0 to 20%. All other drugs were dissolved in distilled water.
Drugs used in this study and their sources were D-amphetamine sulfate [Research Biochemicals (RBI), Natick, MA], apomorphine HCl (RBI), raclopride tartrate (Astra, Sodertalje, Sweden), eticlopride HCl (RBI), (+)-SCH-23390 HCl (RBI), prazosin HCl (RBI), WB4101 HCl (RBI), phenoxybenzamine HCl (RBI), idazoxan HCl (Sigma, St. Louis, MO), propranolole HCl (RBI), nisoxetine HCl (Tocris Cookson, Ballwin, MO), fluoxetine HCl (RBI), and phenylephrine HCl (RBI).
Statistics. The statistical significance of the effect of a drug was determined by comparing the activity of the cell before and after drug injection using ANCOVA followed by a post hoc Tukey test. The covariate was the average of 3 min recordings before the first drug injection (i.e., baseline activity). All numerical data were expressed as mean ± SEM.
RESULTS
The initial finding: rebound of DA neurons after raclopride reversal of D-amphetamine-induced inhibition
In the course of characterizing feedback control of DA neurons, we studied the effect of the selective D2 antagonist raclopride (50 µg/kg) on D-amphetamine (1-2 mg/kg)-induced inhibition of nigral DA neurons (Shi et al. 2000
View larger version (39K):[in this window]
[in a new window]
Figure 1. Excitation of DA neurons after raclopride reversal of D-amphetamine-induced inhibition. A, Representative recordings from a nigral DA neuron showing that raclopride (Rac) not only reversed the inhibition induced by D-amphetamine (Amph) but further increased the activity of the cell to above baseline. Four different parameters were measured: firing rate (spikes/10 sec), number of spikes in bursts (spikes/10 sec), number of bursts (bursts/10 sec), and ISI variation coefficient (percent of mean ISI/10 sec). Of the four measurements, the number of spikes in bursts was increased most significantly. B, Summary of data from eight cells tested with D-amphetamine followed by raclopride. After raclopride, both firing rate and the number of spikes in bursts were significantly increased compared with predrug baseline (F(18,268) = 26.914, p < 0.0005; and F(18,268) = 17.434, p < 0.0005, respectively).
View larger version (63K):[in this window]
[in a new window]
Figure 2. D-Amphetamine excites DA neurons when D2-like receptors are blocked. A, Typical recordings showing that, in a nonanesthetized rat, the activity of a DA cell was also increased after raclopride (Rac) reversal of D-amphetamine (Amph)-induced inhibition. B, Recordings from a different DA neuron showing no significant increase in the activity of the cell after raclopride reversal of the direct DA agonist apomorphine (Apo)-induced inhibition. C, Recordings from another DA cell showing that raclopride alone produced only a small increase in firing. After raclopride, however, D-amphetamine significantly increased both firing rate and bursting. D, Recordings from still another DA neuron showing that the excitatory effect of D-amphetamine persisted after both D1- and D2-like receptors were blocked by SCH23390 (SCH) and eticlopride (Etic).
Raclopride alone produces only a small increase in DA cell activity
To test whether raclopride, by blocking the inhibition induced by spontaneously released DA, can lead to a significant excitation of DA cells, rats were given raclopride (100-200 µg/kg) before D-amphetamine. In most cells tested (16 of 22), raclopride produced only a small effect (<10% of baseline) (Fig. 2C). In the remaining six cells, a >10% increase in firing rate was observed (ranging from 11 to 29%). Overall, the firing rate was increased from 48.1 ± 4.0 to 50.8 ± 4.0 spikes/10 sec after raclopride, whereas the number of spikes in bursts was increased from 7.5 ± 2.8 to 9.7 ± 3.1 spikes/10 sec (n = 22). Both increases, although small, were significant (firing rate, F(19.793) = 6.189, p < 0.0005; bursting, F(19,793) = 1.914, p = 0.011).
D-Amphetamine excites DA cells in raclopride-pretreated rats
To confirm that D-amphetamine has an excitatory effect on DA cells when D2-like receptors are blocked, D-amphetamine (1 mg/kg) was administered after raclopride (100-200 µg/kg). In nearly all cells tested (21 of 22), D-amphetamine produced a marked excitation (Fig. 2C); most cells showed an increase in both firing rate and bursting (n = 15), whereas the remaining cells showed ether an increase in bursting only (n = 4) or an increase in firing rate only (n = 2). In one cell, D-amphetamine produced no effect on firing rate and decreased burst activity by 25%. Altogether, firing rate was increased from 50.8 ± 4.0 to 62.3 ± 3.4 spikes/10 sec, and the number of spikes in bursts was increased from 9.7 ± 3.1 to 27.3 ± 4.2 spikes/10 sec (n = 22). Both increases were highly significant (firing, F(19,793) = 26.9, p < 0.0005; bursting, F(19,793) = 9.5, p < 0.0005).
A similar excitatory effect of D-amphetamine was observed in VTA DA neurons. Thus, after raclopride (50-100 µg/kg), D-amphetamine (1 mg/kg) increased both firing rate and bursting in seven of eight cells tested. In the remaining cell, D-amphetamine produced no effect on either measurement. On average, the firing rate was increased from 60.6 ± 6.6 to 73.2 ± 7.3 spikes/10 sec, and the number of spikes in bursts was increased from 32.3 ± 10.6 to 52.3 ± 11.7 spikes/10 sec (n = 8). Both changes induced by D-amphetamine were statistically significant (firing rate, F(19,275) = 5.015, p < 0.0005; bursting, F(19,275) = 3.255, p < 0.0005).
D-Amphetamine-induced excitation persists after both D1 and D2-like receptors are blocked
By releasing DA, D-amphetamine activates all five subtypes of DA receptors (D1-D5). Raclopride, however, blocks mainly D2 and D3 receptors (Van Tol et al., 1991
Adrenergic
To determine whether part of the excitation induced by D-amphetamine involves activation of adrenergic receptors, the effect of the
View larger version (62K):[in this window]
[in a new window]
Figure 3. The
Pretreatment with prazosin, however, blocked the burst increasing effect of D-amphetamine (Fig. 3A,D). In all seven prazosin-treated rats, D-amphetamine (1 mg/kg), injected after raclopride (100 µg/kg), produced no effect on bursting (from 7.3 ± 4.5 to 7.3 ± 2.9 spikes in bursts/10 sec; F(19,238) = 0.696; p = 0.821; n = 7) (Fig. 3C). In the same cells, D-amphetamine was still able to induce a small increase in firing rate (50.7 ± 3.9 to 55.1 ± 4.0 spikes/10 sec; F(19,238) = 2.2; p < 0.005) (Fig. 3C).
In 10 other cells, prazosin (1 mg/kg) was given after D-amphetamine (1 mg/kg, after 50-100 µg/kg of raclopride). In 7 of 10 cells, the increase in firing induced by D-amphetamine was unaffected or only transiently reversed by prazosin (Fig. 3B). In two cells, the increase was completely reversed by prazosin. In the remaining cell, prazosin partially reversed D-amphetamine-induced increase in firing (69%). The increase in bursting, however, was completely reversed by prazosin in most cells tested (8 of 10) (Fig. 3B). In the remaining two cells, a partial reversal was observed (37 and 64%, respectively).
Similar blocking effects were observed with another
Phenoxybenzamine blocks both
Both prazosin and phenoxybenzamine were dissolved in a PEG solution (4-20%). To test whether PEG has an effect on D-amphetamine-induced excitation, a solution containing PEG only (25-30%, 0.1 ml) was injected after raclopride and D-amphetamine. In all 10 cells tested, no significant effect was observed. In the same cells, subsequent injection of prazosin (n = 3) or phenoxybenzamine (n = 7) reversed the excitation, especially the increase in bursting.
Unlike
The selective norepinephrine uptake blocker nisoxetine mimics the excitatory effect of D-amphetamine
To test further whether selective blockade of norepinephrine (NE) uptake mimics the effect of D-amphetamine, nisoxetine (5-10 mg/kg, i.v.) was administered. In 8 of 12 cells tested, nisoxetine alone increased the activity of the cell (Fig. 4A). In the four remaining cells, nisoxetine produced either a slight decrease or no effect on the activity of the cell. Of the eight cells excited by nisoxetine, five showed an increase in bursting only, two showed an increase in both firing rate and bursting, and one in firing only. Overall, the firing rate was unchanged by nisoxetine (from 49 ± 3.6 to 49 ± 3.9 spikes/10 sec; F(19,423) = 0.38; p = 0.99; n = 12), whereas the number spikes in bursts was significantly increased (from 4.5 ± 3 to 15 ± 4.8 spikes/10 sec; F(19,423) = 6.8; p < 0.0005; n = 12) (Fig. 4C). Subsequent raclopride injection (0.2 mg/kg) further increased both firing rate and bursting in five cells and bursting only in three cells. On average, raclopride increased the firing rate from 49 ± 4.3 to 53 ± 3.8 spikes/10 sec (F(19,423) = 1.9; p < 0.01; n = 12) and the number of spikes in bursts from 15 ± 4.9 to 22 ± 5.4 spikes/10 sec (F(19,423) = 1.2; p = 0.23; n = 12).
View larger version (56K):[in this window]
[in a new window]
Figure 4. The selective NE uptake blocker nisoxetine increases DA cell bursting. A, Typical recordings from a DA cell showing that nisoxetine (Nis) alone produced a significant increase in bursting and a small and transient increase in firing rate. Raclopride (Rac) after nisoxetine further increased firing rate and bursting. The 5-HT uptake blocker fluoxetine (Flu) produced no further effect. Prazosin (Praz) reversed the increase in DA cell activity induced by both nisoxetine and raclopride. B, Recordings from a different DA cell showing that the 5-HT uptake blocker fluoxetine produced no significant effect on either firing rate or bursting. Subsequent injection of raclopride also failed to produce a significant effect. C, Summary of data from all 12 cells tested with nisoxetine (2-5 mg/kg) followed by raclopride (0.1 mg/kg). Nisoxetine had no significant effect on firing rate (left); it, however, significantly increased the number of spikes in bursts (right). Raclopride injection further increased both firing rate and bursting (see Results for detailed statistics).
In six other cells, raclopride was administered before nisoxetine. In most cells (five of six), raclopride alone induced a small increase in firing rate (<10% of baseline). In one cell, raclopride increased bursting from 33 to 44 spikes/10 sec. In five of six raclopride-treated cells, nisoxetine increased bursting. In four cells, this increase in bursting was accompanied with no changes in firing rate. In one cell, firing rate was also increased. In the remaining cell, nisoxetine produced no significant effects. Overall, nisoxetine increased firing rate from 46 ± 7.7 to 50 ± 7.9 spikes/10 sec (F(19,201) = 1.4; p = 0.11) and the number of spikes in bursts from 8.5 ± 7.9 to 20 ± 9.5 spikes/10 sec (F(19,201) = 3.9; p < 0.0005).
To test whether selective blockade of 5-HT uptake also mimics the effect of D-amphetamine, fluoxetine (4 mg/kg) was administered. Of the six cells tested, five showed no significant changes after fluoxetine injection (Fig. 4B). The remaining cell showed a decrease in both firing rate and bursting (from 67 to 56 and 44 to 16 spikes/10 sec, respectively). Overall, the firing rate was reduced from 58 ± 6.2 to 56 ± 6.1 spikes/10 sec (F(19,201) = 1.8; p = 0.024), and the number of spikes in bursts was also slightly reduced from 18 ± 8.2 to 15 ± 6.7 spikes/10 sec (F(19,201) = 0.75; p = 0.76).
In nine other cells, fluoxetine was administered after raclopride (0.2 mg/kg). Six of the cells showed no change, two showed an increase in bursting (from 14 to 24 and from 1.4 to 5.9 spikes/10 sec, respectively), and the remaining cell showed a decrease in bursting (from 11 to 1.4 spikes/10 sec). On average, the firing rate was slightly decreased by fluoxetine (from 57 ± 3.3 to 56 ± 3.1 spikes/10 sec), whereas the number spikes in bursts was slightly increased (from 15 ± 2.8 to 16 ± 3.2 spikes/10 sec). Both changes were statistically insignificant (firing rate, F(19,312) = 0.56, p = 0.93; bursting, F(19,312) = 0.84, p = 0.66).
To test whether fluoxetine excites DA cells when both NE uptake and D2-like receptors are blocked, rats were given nisoxetine (10 mg/kg) and raclopride (0.2 mg/kg), and then fluoxetine (4-8 mg/kg). In seven of nine cells tested, fluoxetine produced no significant effect (Fig. 4A). In one cell, however, both firing rate and bursting were increased after fluoxetine (firing rate, from 47 to 58 spikes/10 sec; bursting, from 21 to 45 spikes/10 sec). In the remaining cell, fluoxetine increased firing rate only (from 58 to 71 spikes/10 sec). Overall, the effects of fluoxetine were insignificant (firing rate, from 53 ± 4.1 to 56 ± 4.3, F(19,312) = 1.2, p = 0.25; bursting, from 21 ± 6.5 to 27 ± 7.4, F(19,312) = 0.697, p = 0.82).
The prepheral
When administered systemically, D-amphetamine increases NE release both peripherally and centrally. To test whether peripheral
View larger version (70K):[in this window]
[in a new window]
Figure 5. Effects of peripheral activation of
DISCUSSION
The present study shows that systemic administration of D-amphetamine has two opposing effects on DA neurons: a DA-mediated feedback inhibition and a non-DA-mediated excitation. Evidence further suggests that the excitatory effect is mediated in part through adrenergic
The inhibitory effect of D-amphetamine on DA cells has been extensively studied. Evidence suggests that the effect involves release of endogenous DA and activation of DA receptors (Bunney and Aghajanian, 1976
D-Amphetamine, by releasing endogenous DA, should activate all subtypes of DA receptors (D1-D5). Raclopride, however, blocks mainly D2 and D3 receptors, raising the possibility that D-amphetamine excites DA cells through DA receptors not blocked by raclopride, i.e., D1, D4, or D5 receptors. Our results suggest, however, that D-amphetamine-induced excitation is not a DA receptor-mediated effect because it persisted after injections of both SCH23390 and eticlopride, a treatment that should block all subtypes of DA receptors. The excitation was largely blocked, however, by adrenergic
D-Amphetamine also binds to 5-HT uptake transporters. The affinity, however, is lower compared with that for DA or NE transporters (Ritz and Kuhar, 1989
During D-amphetamine-induced excitation, most cells showed increases in both firing rate and bursting. Several observations suggest that two changes may be mediated by different mechanisms. Thus, in many cells, the increase in firing rate was only partially blocked or not affected by an
When administered systemically, D-amphetamine increases release of NE both peripherally and centrally. Our data suggest that the excitatory effect of D-amphetamine is centrally mediated because (1) the effect persisted after a complete brainstem transection, which should block all visceral input as well as most somatosensory input to the brain, and (2) selective activation of peripheral
The finding that D-amphetamine excites DA cells in part through adrenergic receptors may have important clinical implications. In preliminary studies, we have found that the excitatory effect of D-amphetamine is mimicked by all psychostimulants tested, including cocaine, methamphetamine, and methylphenidate (Shi et al., 1999
Pathways responsible for the adrenergic excitation of DA neurons may be activated by mechanisms other than psychostimulants. It is well known that NE neurons in the locus ceruleus are particularly sensitive to stress (Abercrombie and Jacobs, 1987
FOOTNOTES Received Dec. 21, 1999; revised Feb. 23, 2000; accepted Feb. 23, 2000.
This work was supported in part by United States Public Health Service Grants MH52686 (W.-X.S), DA12944 (W.-X.S), and MH28849 (B.S.B), and the State of Connecticut.
Correspondence should be addressed to Dr. Wei-Xing Shi, Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, SHM B-272, P.O. Box 208066, New Haven, CT 06520. E-mail address: wei-xing.shi{at}yale.edu.
REFERENCES
- Abercrombie ED, Jacobs BL (1987) Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and nonstressful stimuli. J Neurosci 7:2837-2843[Abstract].
- Alexander BS, Wood MD (1987) Stereoselective blockade of central [3H]5-hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B and 5-HT1C) by mianserin and propranolol. J Pharm Pharmacol 39:664-666[Medline].
- Bunney BS, Aghajanian GK (1976) d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science 192:391-393
[Abstract/Free Full Text] .- Bunney BS, Aghajanian GK (1978) d-Amphetamine-induced depression of central dopamine neurons: evidence for mediation by both autoreceptors and a striato-nigral feedback pathway. Naunyn Schmiedebergs Arch Pharmacol 304:255-261[Web of Science][Medline].
- Bunney BS, Walters JR, Roth RH, Aghajanian GK (1973) Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185:560-571
[Abstract/Free Full Text] .- Collingridge GL, James TA, MacLeod NK (1979) Neurochemical and electrophysiological evidence for a projection from the locus coeruleus to the substantia nigra. J Physiol (Lond) 290:44P[Medline].
- Darracq L, Blanc G, Glowinski J, Tassin JP (1998) Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamine. J Neurosci 18:2729-2739
[Abstract/Free Full Text] .- Einhorn LC, Johansen PA, White FJ (1988) Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area. J Neurosci 8:100-112[Abstract].
- Finlay JM, Zigmond MJ (1997) The effects of stress on central dopaminergic neurons: possible clinical implications. Neurochem Res 22:1387-1394[Web of Science][Medline].
- Gao WY, Lee TH, King GR, Ellinwood EH (1998) Alterations in baseline activity and quinpirole sensitivity in putative dopamine neurons in the substantia nigra and ventral tegmental area after withdrawal from cocaine pretreatment. Neuropsychopharmacology 18:222-232[Web of Science][Medline].
- Gariano RF, Groves PM (1988) Burst firing induced in midbrain dopamine neurons by stimulation of the medial prefrontal and anterior cingulate cortices. Brain Res 462:194-198[Web of Science][Medline].
- Grace AA, Bunney BS (1980) Nigral dopamine neurons: intracellular recording and identification with L-dopa injection and histofluorescence. Science 210:654-656
[Abstract/Free Full Text] .- Grace AA, Bunney BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons. I. Identification and characterization. Neuroscience 10:301-315[Web of Science][Medline].
- Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4:2877-2890[Abstract].
- Grenhoff J, Svensson TH (1993) Prazosin modulates the firing pattern of dopamine neurons in rat ventral tegmental area. Eur J Pharmacol 233:79-84[Web of Science][Medline].
- Grenhoff J, Nisell M, Ferre S, Aston-Jones G, Svensson TH (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J Neural Transm Gen Sect 93:11-25[Web of Science][Medline].
- Grenhoff J, North RA, Johnson SW (1995) Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice. Eur J Neurosci 7:1707-1713[Web of Science][Medline].
- Henry DJ, Hu XT, White FJ (1998) Adaptations in the mesoaccumbens dopamine system resulting from repeated administration of dopamine D1 and D2 receptor-selective agonists: relevance to cocaine sensitization. Psychopharmacology (Berl) 140:233-242[Medline].
- Kamata K, Rebec GV (1984) Long-term amphetamine treatment attenuates or reverses the depression of neuronal activity produced by dopamine agonists in the ventral tegmental area. Life Sci 34:2419-2427[Web of Science][Medline].
- Lee TH, Gao WY, Davidson C, Ellinwood EH (1999) Altered activity of midbrain dopamine neurons following 7-day withdrawal from chronic cocaine abuse is normalized by D2 receptor stimulation during the early withdrawal phase. Neuropsychopharmacology 21:127-136[Medline].
- Murase S, Grenhoff J, Chouvet G, Gonon FG, Svensson TH (1993) Prefrontal cortex regulates burst firing and transmitter release in rat mesolimbic dopamine neurons studied in vivo. Neurosci Lett 157:53-56[Web of Science][Medline].
- Prisco S, Esposito E (1995) Differential effects of acute and chronic fluoxetine administration on the spontaneous activity of dopaminergic neurones in the ventral tegmental area. Br J Pharmacol 116:1923-1931[Web of Science][Medline].
- Ritz MC, Kuhar MJ (1989) Relationship between self-administration of amphetamine and monoamine receptors in brain: comparison with cocaine. J Pharmacol Exp Ther 248:1010-1017
[Abstract/Free Full Text] .- Shi WX, Pun CL, Jones M, Bunney BS (1997a) An
- Shi WX, Smith PL, Pun CL, Millet B, Bunney BS (1997b) D1-D2 interaction in feedback control of midbrain dopamine neurons. J Neurosci 17:7988-7994
[Abstract/Free Full Text] .- Shi WX, Pun CL, Jones M, Bunney BS (1998) d-Amphetamine-induced excitation of midbrain DA neurons: an effect mediated by
- Shi WX, Pun C-L, Zhang X-X, Smith PL, Jones MD (1999) Opposite effects of psychostimulants on DA neurons mediated by DA and non-DA receptors. Soc Neurosci Abstr 25:1820.
- Shi WX, Pun C-L, Smith PL, Bunney BS (2000) Endogenous DA-mediated feedback inhibition of midbrain DA neurons: involvement of both D1- and D2-like receptors. Synapse 35:111-119[Medline].
- Stone EA, Zhang Y (1995) Adrenoceptor antagonists block c-fos response to stress in the mouse brain. Brain Res 694:279-286[Medline].
- Tong ZY, Overton PG, Clark D (1996) Stimulation of the prefrontal cortex in the rat induces patterns of activity in midbrain dopaminergic neurons which resemble natural burst events. Synapse 22:195-208[Web of Science][Medline].
- Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610-614[Medline].
- White FJ, Wang RY (1984) Electrophysiological evidence for A10 dopamine autoreceptor subsensitivity following chronic D-amphetamine treatment. Brain Res 309:283-292[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] .- Zhang X-X, Pun C-L, Bunney BS, Shi W-X (1999) Adrenergic a1-mediated increase in bursting of DA neurons: role of glutamate. Soc Neurosci Abstr 25:1819.
Copyright © 2000 Society for Neuroscience 0270-6474/00/2093504-08$05.00/0
This article has been cited by other articles:
D. M. Platt, J. K. Rowlett, and R. D. Spealman
Noradrenergic Mechanisms in Cocaine-Induced Reinstatement of Drug Seeking in Squirrel Monkeys
J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 894 - 902.
[Abstract] [Full Text] [PDF]
M. Gao, C.-L. Liu, S. Yang, G.-Z. Jin, B. S. Bunney, and W.-X. Shi
Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area
J. Neurosci., May 16, 2007; 27(20): 5414 - 5421.
[Abstract] [Full Text] [PDF]
G. Cui, B. E. Bernier, M. T. Harnett, and H. Morikawa
Differential Regulation of Action Potential- and Metabotropic Glutamate Receptor-Induced Ca2+ Signals by Inositol 1,4,5-Trisphosphate in Dopaminergic Neurons
J. Neurosci., April 25, 2007; 27(17): 4776 - 4785.
[Abstract] [Full Text] [PDF]
R. Ventura, C. Morrone, and S. Puglisi-Allegra
Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli
PNAS, March 20, 2007; 104(12): 5181 - 5186.
[Abstract] [Full Text] [PDF]
L. Salomon, C. Lanteri, J. Glowinski, and J.-P. Tassin
Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neurons
PNAS, May 9, 2006; 103(19): 7476 - 7481.
[Abstract] [Full Text] [PDF]
Y. Zhou, B. S. Bunney, and W.-X. Shi
Differential Effects of Cocaine on Firing Rate and Pattern of Dopamine Neurons: Role of {alpha}1 Receptors and Comparison with L-Dopa and Apomorphine
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 196 - 201.
[Abstract] [Full Text] [PDF]
R. Ventura, A. Alcaro, and S. Puglisi-Allegra
Prefrontal Cortical Norepinephrine Release Is Critical for Morphine-induced Reward, Reinstatement and Dopamine Release in the Nucleus Accumbens
Cereb Cortex, December 1, 2005; 15(12): 1877 - 1886.
[Abstract] [Full Text] [PDF]
W.-X. Shi
Slow Oscillatory Firing: A Major Firing Pattern of Dopamine Neurons in the Ventral Tegmental Area
J Neurophysiol, November 1, 2005; 94(5): 3516 - 3522.
[Abstract] [Full Text] [PDF]
C. A. Paladini, J. M. Mitchell, J. T. Williams, and G. P. Mark
Cocaine Self-Administration Selectively Decreases Noradrenergic Regulation of Metabotropic Glutamate Receptor-Mediated Inhibition in Dopamine Neurons
J. Neurosci., June 2, 2004; 24(22): 5209 - 5215.
[Abstract] [Full Text] [PDF]
E. A. Budygin, M. S. Brodie, T. D. Sotnikova, Y. Mateo, C. E. John, M. Cyr, R. R. Gainetdinov, and S. R. Jones
Dissociation of rewarding and dopamine transporter-mediated properties of amphetamine
PNAS, May 18, 2004; 101(20): 7781 - 7786.
[Abstract] [Full Text] [PDF]
C. A. Paladini and J. T. Williams
Noradrenergic Inhibition of Midbrain Dopamine Neurons
J. Neurosci., May 12, 2004; 24(19): 4568 - 4575.
[Abstract] [Full Text] [PDF]
K.-C. Choong and R.-Y. Shen
Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission
J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 444 - 451.
[Abstract] [Full Text] [PDF]
R. Ventura, S. Cabib, A. Alcaro, C. Orsini, and S. Puglisi-Allegra
Norepinephrine in the Prefrontal Cortex Is Critical for Amphetamine-Induced Reward and Mesoaccumbens Dopamine Release
J. Neurosci., March 1, 2003; 23(5): 1879 - 1885.
[Abstract] [Full Text] [PDF]
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]
L. K. Tremblay, C. A. Naranjo, L. Cardenas, N. Herrmann, and U. E. Busto
Probing Brain Reward System Function in Major Depressive Disorder: Altered Response to Dextroamphetamine
Arch Gen Psychiatry, May 1, 2002; 59(5): 409 - 416.
[Abstract] [Full Text] [PDF]
C. Drouin, L. Darracq, F. Trovero, G. Blanc, J. Glowinski, S. Cotecchia, and J.-P. Tassin
alpha 1b-Adrenergic Receptors Control Locomotor and Rewarding Effects of Psychostimulants and Opiates
J. Neurosci., April 1, 2002; 22(7): 2873 - 2884.
[Abstract] [Full Text] [PDF]
L. R. McMahon, M. Filip, and K. A. Cunningham
Differential Regulation of the Mesoaccumbens Circuit by Serotonin 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors
J. Neurosci., October 1, 2001; 21(19): 7781 - 7787.
[Abstract] [Full Text] [PDF]
L. Linnér, H. Endersz, D. Öhman, F. Bengtsson, M. Schalling, and T. H. Svensson
Reboxetine Modulates the Firing Pattern of Dopamine Cells in the Ventral Tegmental Area and Selectively Increases Dopamine Availability in the Prefrontal Cortex
J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 540 - 546.
[Abstract] [Full Text]
C. Xu and R.-Y. Shen
Amphetamine Normalizes the Electrical Activity of Dopamine Neurons in the Ventral Tegmental Area following Prenatal Ethanol Exposure
J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 746 - 752.
[Abstract] [Full Text]
This Article Abstract 
Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager 
Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (69) Citing Articles via Google Scholar Google Scholar Articles by Shi, W.-X. Articles by Bunney, B. S. Search for Related Content PubMed PubMed Citation Articles by Shi, W.-X. Articles by Bunney, B. S.
|
|
|
|
 |
|