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The Journal of Neuroscience, May 1, 2001, 21(9):3251-3260
The Role of the Nucleus Accumbens in Instrumental Conditioning:
Evidence of a Functional Dissociation between Accumbens Core and
Shell
Laura H.
Corbit1,
Janice L.
Muir2, and
Bernard W.
Balleine1
1 Department of Psychology, University of California
Los Angeles, Los Angeles, California 90095, and 2 School of
Psychology, Cardiff University, Cardiff, CF10 3YG, United Kingdom
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ABSTRACT |
In three experiments we examined the effect of bilateral
excitotoxic lesions of the nucleus accumbens core or shell subregions on instrumental performance, outcome devaluation, degradation of
the instrumental contingency, Pavlovian conditioning, and
Pavlovian-instrumental transfer. Rats were food deprived and trained to
press two levers, one delivering food pellets and the other a sucrose
solution. All animals acquired the lever-press response although the
rate of acquisition and overall response rates in core-lesioned animals were depressed relative to that in the shell- or sham-lesioned animals.
Furthermore, in shell- and sham-lesioned rats, post-training devaluation of one of the two outcomes using a specific satiety procedure produced a selective reduction in performance on the lever
that, in training, delivered the prefed outcome. In contrast, the
core-lesioned rats failed to show a selective devaluation effect
and reduced responding on both levers. Subsequent tests revealed that
these effects of core lesions were not caused by an impairment in their
ability to recall the devalued outcome, to discriminate the two
outcomes, or to encode the instrumental action-outcome contingencies
to which they were exposed. Additionally, the core lesions did not have
any marked effect on Pavlovian conditioning or on
Pavlovian-instrumental transfer. Importantly, although shell-lesioned rats showed no deficit in any test of instrumental conditioning or in
Pavlovian conditioning, they failed to show any positive transfer in
the Pavlovian-instrumental transfer test. This double dissociation
suggests that nucleus accumbens core and shell differentially mediate
the impact of instrumental and Pavlovian incentive processes, respectively, on instrumental performance.
Key words:
nucleus accumbens; core; shell; instrumental
conditioning; Pavlovian conditioning; Pavlovian-instrumental transfer; devaluation; contingency; incentive; reward
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INTRODUCTION |
The neural processes mediating
reward and reinforcement have received considerable research attention
(Robbins and Everitt, 1996 ). However, these studies have
generally been conducted without consideration of how these reward
processes interact with structures that mediate instrumental behavior,
and as a consequence, their role in instrumental learning remains to be identified.
Several lines of evidence suggest that the nucleus accumbens (NAC) may
play an important role in relating reward processes to the
action-outcome associations that underlie instrumental learning (cf.
Colwill and Rescorla, 1986; Dickinson and Balleine, 1994). Anatomical
studies have revealed that the NAC receives excitatory glutamatergic
afferents from "limbic" structures such as the basolateral
amygdala, the ventral subiculum, and the medial prefrontal cortices
(Powell and Leman, 1976; Kelley and Domesick, 1982; Kelley et al.,
1982; Alheid and Heimer, 1988). It also receives dopaminergic inputs
from the ventral tegmental area and is a major component of the
mesolimbic dopamine system (Moore and Bloom, 1978). On the basis of
such anatomical findings, Mogenson and colleagues advanced the
influential suggestion that the NAC may be a central structure in the
control of action, reflecting an area of limbic-motor integration
(Mogenson et al., 1980, 1988; Mogenson and Yim, 1991). From this
perspective, limbic inputs to the accumbens carrying associative and
motivational information were argued to influence motor activity via an
accumbens-pallidal pathway and the projections of the latter structure
to the mesencephalic locomotor region (Groenewegen and Russchen, 1984;
Nauta and Domesick, 1984; Haber et al., 1985).
The NAC itself is a heterogeneous structure and can be further divided
into anatomically distinct core and shell subregions (Zahm and Brog,
1992). Both core and shell receive inputs from the amygdala, globus
pallidus, and ventral pallidum. However, they differ in the density of
their cortical afferents; the core receives projections predominantly
from the prelimbic, anterior cingulate, and dorsal agranular insular
cortices, and the shell receives projections predominantly from
infralimbic, ventral agranular insular, and piriform cortices (Zahm and
Brog, 1992; Zahm, 2000). Perhaps more important, the efferents of these
regions differ substantially; the core projects to conventional basal
ganglia circuitry including the ventral pallidum, globus pallidus, and the substantia nigra, whereas the shell projects to subcortical limbic
structures such as the lateral hypothalamus, the ventral tegmental
area, and the ventromedial ventral pallidum (Zahm and Brog,
1992). These differences in connections raise the possibility that
these two regions of the accumbens may be functionally independent.
A number of studies have demonstrated that lesions of the NAC act to
reduce instrumental performance (Balleine and Killcross, 1994), a
finding that has been confirmed using more selective manipulations of
glutamatergic (Kelley et al., 1997) and dopaminergic (Sokolowski and
Salamone, 1998) activity. The general aim of the current study was to
characterize more fully the role of the NAC in instrumental
conditioning. Specifically, the impact of lesions of the NAC core and
shell on instrumental behavior after outcome devaluation, after
contingency degradation, and in a Pavlovian-instrumental transfer test
was examined.
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MATERIALS AND METHODS |
Experiment 1: outcome devaluation by specific satiety
Subjects and apparatus
The subjects were 24 experimentally naïve female
Long-Evans rats. The rats were housed singly and were handled daily
for 1 week before surgery. Training and testing took place in 16 Med Associates (East Fairfield, VT) operant chambers housed within sound-
and light-resistant shells. Each chamber was equipped with a pump
fitted with a syringe that delivered 0.1 ml of a 20% sucrose solution
into a recessed magazine in the chamber. Each chamber was also
equipped with a pellet dispenser that delivered one 45 mg Noyes pellet
(formula A/I) when activated. The chambers contained two retractable
levers that could be inserted to the left and right of the
magazine. A 3 W, 24 V house light mounted on the top-center of the wall
opposite the magazine provided illumination. Microcomputers equipped
with the MED-PC program (Med Associates) controlled the equipment and
recorded the lever presses.
Surgery
At the time of surgery, animals weighed between 266 and 338 gm.
There were three surgical groups; rats received cell body lesions of
either the core or shell region of the nucleus accumbens or sham
surgery. Rats were anesthetized using sodium pentobarbital (Nembutal,
50 mg/kg), treated with atropine (0.1 mg), and then placed in a
stereotaxic frame (Stoelting Company, Wood Dale, IL) with the incisor
bar set at  3.3 mm. The scalp was retracted to expose the skull, and
small burr holes were drilled above the target regions. For lesions of
the core (n = 7), animals received bilateral injections
of 0.5 µl of 0.12 M NMDA in two sites
(one per side) using a 1 µl Hamilton syringe (all coordinates in
millimeters relative to bregma; anteroposterior, +1.2;
mediolateral, ±2.1; and dorsoventral, 7.0). Each injection
was made over 2 min and allowed to diffuse for an additional 2 min
before removal of the needle. For lesions of the shell region
(n = 9), animals received 0.2 µl injections of 0.015 M AMPA hydrobromide at four sites (two per
side, anteroposterior, +1.6; mediolateral, ±0.8; and dorsoventral, 6.8, 6.0). Injections were again made over 2 min with an
additional 2 min allowed before any movement of the needle. Animals in
the surgical control group (n = 8) underwent similar
treatment except that no neurotoxin was injected.
Histology
At the end of the experiment, the animals were killed using a
lethal barbiturate overdose and perfused transcardially with 0.9%
saline followed by 10% formaldehyde solution. The brains were stored
in 10% formalin solution for at least 48 hr and then transferred to a
25% sucrose-formalin solution before 40 µm coronal sections were
cut throughout the region of the nucleus accumbens. Alternate slices
were stained using thionin. Slides were examined for placement and
extent of the lesion; the latter was assessed by microscopically
examining sections for areas of marked cell loss as well as general
shrinkage of a region relative to sham controls.
Procedure
Training. After recovery from surgery, subjects were
placed on a food deprivation schedule such that they received 15 gm of their maintenance diet daily to maintain them at ~85% of their free-feeding weight. The animals were fed each day after the training sessions. Animals were provided tap water ad libitum
while in the home cage. Each session started with the illumination of
the house light and insertion of the levers where appropriate and ended
with the retraction of the levers and turning off of the house light.
All sessions were 30 min in duration unless otherwise stated.
Magazine training. Initially, all subjects received two
sessions of magazine training in which the pellet and sucrose outcomes were delivered on independent random time (RT) 60 sec schedules with
the levers withdrawn.
Lever training. The animals were next trained on random
ratio (RR) schedules of reinforcement. Each lever was trained
separately, and for half of the animals in each group, the left lever
earned pellets and the right lever earned the sucrose solution. The
remaining animals received the opposite action-outcome pairings. The
animals first received 1 d of continuous reinforcement and
were then shifted to an RR-5 schedule (i.e., each action delivered an
outcome with a probability of 0.2). After 3 d of training this was
changed to an RR-10 schedule (or a probability of 0.1) for 3 d and
then to an RR-20 schedule (or a probability of 0.05) for an additional 3 d of training. The animals received two training sessions each day, one with each action-outcome pair. The animals had a break of at
least 1 hr between sessions, and the order was alternated each day.
Devaluation extinction tests. After the final day of RR-20
training, all of the rats were given access ad libitum to
one of the two outcomes for 1 hr in the home cage. Half of the animals in each action-outcome pair assignment received pellets (50 gm placed
in a bowl in the home cage), and the remaining animals received sucrose
(50 ml in a drinking bottle fixed to the front of the home cage).
Immediately after the prefeeding, the animals were placed in the
operant chambers. A 10 min choice extinction test was then conducted in
which both levers were extended and the number of presses was counted
on each lever. No outcomes were delivered during the test. After the
first devaluation test, the animals received 1 d of retraining
(RR-20; one session for each action-outcome pair) and were then given
a second devaluation test on the following day. The second test was
identical to the first except that those animals that had had pellets
devalued previously now had sucrose devalued and those that had had
sucrose devalued were now prefed pellets.
Reward test. After the second devaluation test conducted in
extinction, the animals were retrained (RR-20; one 30 min session for
each action-outcome pair) and on the following day tested for their
sensitivity to the devaluation manipulation when performance was
rewarded. This test was conducted in the same manner as the extinction
test except that the outcomes were delivered as a consequence of
instrumental performance. In this 20 min session, the two outcomes were
delivered according to independent ratio schedules (RR-20).
Experiment 2: contingency degradation
Subjects and apparatus
The subjects and general apparatus are as described for
experiment 1.
Procedure
Contingency degradation training. After the
devaluation tests, the rats received 2 d of retraining on RR-20
schedules before the selective degradation of one of the instrumental
contingencies. At the end of training, each lever press earned a unique
outcome (pellets or a 20% sucrose solution) with a fixed probability
[p(outcome/action) = 0.05]. The rats continued to
be trained on the two actions with the appropriate paired outcomes, but
in addition to being earned by one of the actions, one of the outcomes
was now also delivered noncontingently with the same probability
[p(outcome/no action) = 0.05] in each second
without a response. For one lever, the noncontingent or free
reinforcer was the same as that earned by a response on that lever.
Thus, the experienced probability of the delivery of that particular
outcome was the same whether or not the animals performed that action,
a procedure that should act to degrade that specific action-outcome
contingency. For the other lever, the free reinforcer was different
from the earned reinforcer, and so this contingency was not degraded.
For half of the animals the lever press-pellet contingency was
degraded, whereas for the remainder the lever press-sucrose
contingency was degraded. The rats were given two 20 min training
sessions each day, one on each lever with a break of ~2 hr between
sessions. The order of the sessions was alternated each day and
training continued for 8 d.
Contingency degradation extinction test. On the day after
the final day of contingency training, rats in both groups received a
choice extinction test. The test began with the insertion of both
levers and the onset of the house light and ended 10 min later with the
retraction of the levers and the offset of the house light. No outcomes
were presented during this session.
Experiment 3: Pavlovian-instrumental transfer
Subjects and apparatus
The subjects and apparatus are as described for experiment 1.
Procedure
Pavlovian training. Initially the animals were
retrained for 3 d on RR-20 schedules after the contingency
extinction test. Next the animals received eight sessions of Pavlovian
conditioning. Two 80 dB auditory stimuli (tone and white noise) served
as conditioned stimuli (CSs) and were paired with either pellet or
sucrose delivery. For half of each lesion condition, the tone was
paired with pellet delivery, and the noise was paired with sucrose
delivery. The remaining half received the reverse pairings. Four
presentations of each stimulus were given in each session in random
order interspersed with periods in which no stimuli were present. The
length of the intertrial intervals varied, but on average these
intervals were 5 min. The stimuli presentations were 2 min long during
which the appropriate outcome was delivered on an RT 30 sec schedule. The number of magazine entries during the stimuli as well as in a
prestimulus interval of equal length (2 min) was measured. After 8 d of stimulus training, the animals were retrained with the levers for
1 d on the RR-20 schedule before testing.
Pavlovian-instrumental transfer test. The animals received
two extinction tests (one on each lever) 1 d apart. During each test one of the levers was available, and each stimulus was presented four times interspersed with intervals of no stimulus (Ø). Each test
was 32 min in duration. In the first 8 min the levers were available,
but no stimuli were presented. This period was followed by 12 bins of 2 min each and contained a total of eight stimulus trials [four tone
trials (T) and four noise trials (N) intermixed with four Ø trials in
the following order: Ø, T, N, Ø, N, T, Ø, N, T, Ø, T, and N].
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RESULTS |
Experiment 1: outcome devaluation
The aim of experiment 1 was to assess the impact of lesions of
the NAC core or shell on instrumental learning by assessing the
impact of these lesions on training and, subsequently, on the
sensitivity of the performance of the rat to the effects of outcome
devaluation using a specific satiety treatment (Adams and Dickinson,
1981; Balleine and Dickinson, 1998b). It has been shown that this
treatment induces a selective reduction in the current incentive value
of the prefed outcome (Balleine and Dickinson, 1998b), and so, in
agreement with previous findings, we anticipated that sham rats would
show an outcome devaluation effect reflected in fewer responses being
performed on the lever that, in training, delivered the now-devalued
outcome. However, if the NAC is required for either the encoding of the
incentive value of an instrumental outcome or the formation of
action-outcome associations during instrumental training, then any
outcome devaluation effect established in sham controls should be
severely attenuated in the lesioned groups.
Histology
No recovery problem or weight loss was observed after surgery.
Figure 1 displays the maximum and minimum
damage resulting from the lesions for the animals included in the
behavioral analyses of the core (A) and shell
(B) based on the stereotaxic atlas of the rat
brain by Paxinos and Watson (1998). Any animals with unilateral damage
or damage outside the target region were excluded from the behavioral
analyses. Figure 2 displays
photomicrographs taken of representative lesions of the sham
(right images), core (top images), and
shell (bottom images) groups. The photographs on the right in Figure 2 show magnifications of the lesions
shown in the images on the left. Magnifications
of the sham brain in the region of the core and shell are shown for
comparison in the top right and bottom right
images, respectively, of Figure 2. Core lesions (Fig. 2, top
images) resulted in substantial neuronal loss in the core region
bilaterally and typically extended in the anteroposterior direction
from 0.7 to 1.7 mm anterior to bregma. Generally the lesion did not
extend ventrally to the ventral pallidum or dorsally to the
caudate-putamen. Any animals with marked damage to the NAC shell were
excluded from the behavioral analysis. NAC shell lesions (Fig. 2,
bottom images) destroyed neurons in the mediodorsal shell
bilaterally and typically extended in the anteroposterior direction
from 1.0 to 1.7 mm anterior to bregma. The ventral and ventrolateral
portions of the NAC shell appeared unaffected by the lesions. Any
animals with substantial damage of the NAC core or any other
surrounding structures outside the shell were excluded.
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Figure 1.
Schematic representation of excitotoxic lesions of
the NAC core (A) and shell
(B). Shaded areas represent the
maximum (black) and minimum (gray)
extent of the lesions for the animals included in the behavioral
analyses. Coronal sections are taken from the following points in the
anteroposterior plane beginning at top left: +2.2, +1.7,
+1.6, +1.2, +1.0, and +0.7 mm anterior to bregma (Paxinos and
Watson, 1998).
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Figure 2.
Photomicrographs showing thionin-stained coronal
sections through the nucleus accumbens. Top,
Representative core lesions. Bottom, Representative
shell lesions. Left, Images of the
general region of the NAC (40× magnification) of core-lesioned
(top) and shell-lesioned (bottom)
animals. Middle, Greater magnification of the region
indicated by the outlined boxes in the left
images; arrowheads indicate lesion boundaries.
Right, High-magnification photographs of
the region of the lesions shown in the middle images (in
lesioned animals) but in sham-lesioned animals. All
images are from slices taken at ~2.6 mm anterior to
bregma. ac, Anterior commissure; Co, NAC
core; LV, lateral ventricle; Sh, NAC
shell.
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Training
As shown in Figure 3, animals from
each group acquired the lever-press response for the two outcomes, and
their response rates increased as the ratio schedule parameter
increased across days. Nevertheless, the groups clearly diverged in
their performance during training; the core-lesioned rats performed at
a generally lower rate and the shell-lesioned rats performed at a
slightly higher rate than did the sham-lesioned rats. Initial
statistical analysis revealed that there was no effect of outcome type
(F < 1), and so the data were collapsed across outcome
for presentation and subsequent analysis. ANOVA revealed a
significant effect of training day
[F(8,16) = 13.205; p < 0.01]. Also, as indicated by Figure 3, a significant effect of
group confirms that the groups responded at different rates
[F(2,21) = 6.907; p < 0.01]. Additionally there was a marginal day × group
interaction suggesting that, at least numerically, the increase in
responding across days differed between the three groups
[F(16,168) = 1.655; p = 0.06]. Tukey pairwise comparisons conducted on the mean rate of
performance during training revealed that the core-lesioned group
responded at a reliably lower rate than did both the sham- and the
shell-lesioned groups (p < 0.01). The numerical
difference observed between the shell- and sham-lesioned groups failed
to achieve significance (p > 0.05).
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Figure 3.
Mean lever-press responses per minute for the
three groups across days of training. Responding was reinforced on days
1-3 on an RR-5 schedule of reinforcement, on days 4-6 on an RR-10
schedule of reinforcement, and on days 7-9 on an RR-20 schedule of
reinforcement.
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Devaluation extinction tests
Mean lever presses per minute during the choice extinction test
are presented in Figure 4 collapsed
across the two tests. Inspection of Figure 4 reveals a clear
devaluation effect in both the sham- and shell-lesioned rats. However,
the core animals show a very different pattern of responding,
decreasing responding on both levers. A two-way ANOVA conducted using
factors of group, separating the three lesion conditions, and of
devaluation, separating performance on the lever that, in training,
delivered the now-devalued outcome from responding on the other lever,
revealed a significant main effect of group
[F(2,21) = 6.223;
p < 0.01], an effect of devaluation
[F(1,21) = 26.696; p < 0.01], and more important, a significant group × devaluation interaction [F(1,21) = 4.821; p < 0.05]. Simple effects analyses revealed
that, although a significant effect of devaluation emerged in both the
sham-lesioned [F(1,21) = 24.581;
p < 0.01] and shell-lesioned
[F(1,21) = 13.244; p < 0.01] rats, core-lesioned rats did not respond differently on the two levers; thus whereas the devaluation manipulation clearly affects their lever-press performance, the core-lesioned animals fail to show a selective devaluation effect
[F(1,21) < 1].
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Figure 4.
Mean lever-press responses for the devaluation
tests conducted in experiment 1 for each of the lesioned groups.
A, Sham. B, Shell. C,
Core. For A-C, the left panel displays
the mean response rate per minute at the end of training. The
second panel from the left displays
responses per minute for the devalued and nondevalued outcomes in a
two-lever, choice extinction test. The third panel from
the left illustrates the mean performance during the
retraining sessions, and the right panel displays the
mean lever-press responses per minute in a rewarded, two-lever test
after devaluation of one of the instrumental outcomes.
SED represents the SE of the difference in
responding for the within-subjects variable. DEV,
Devalued; NON, nondevalued.
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Reward test
The failure of core-lesioned rats to show a selective devaluation
effect could be explained in several ways. It could be that the core
region of the accumbens is critical for encoding the value of different
outcomes, or alternatively, it could be that the memory of the two
outcomes is impaired. If animals are unable to differentiate the two
outcomes in extinction, then devaluation of one outcome may generalize
to the other resulting in a decrease in performance of both responses.
To assess whether the deficit observed in the extinction test was
caused by a failure to discriminate the outcomes in extinction rather
than in devaluation per se, the animals were retrained and tested again
for their sensitivity to outcome devaluation but this time with the two
outcomes being delivered. Because the two outcomes are delivered in
this test, any deficit observed in the core group cannot be attributed
to failure to remember and distinguish the two outcomes but, rather, would suggest a deficit in the instrumental incentive processes that
mediate outcome devaluation. The results of this test are presented in
the right panels of Figure 4. Generally, the pattern of
results in the reward test was similar to those results observed in the
extinction test; sham- and shell-lesioned rats showed strong selective
devaluation effects, whereas core-lesioned rats failed to show any
selective effect of the devaluation treatment. The statistical analysis
revealed significant main effects of devaluation [F(1,21) = 9.752;
p < 0.01] and group
[F(2,21) = 5.205; p < 0.05], and again, simple effects analyses found that, although the
devaluation effect was reliable in the sham-lesioned
[F(1,21) = 9.447; p < 0.01] and shell-lesioned [F(1,21) = 6.171; p < 0.01] rats, even when the outcomes were
delivered, the core-lesioned rats failed to show a selective
devaluation effect [F(1,21) < 1]
and performed very few responses on either lever. This suggests that
the deficit in the core animals, observed both when tested in
extinction and when performance is rewarded, is caused by a failure of
the current incentive values of the instrumental outcomes to control
performance selectively. Clearly the incentive value of the nondevalued
outcome was unable to maintain instrumental responding in the
core-lesioned group.
In addition to leaning the value of the instrumental outcome,
considerable evidence suggests that, in instrumental conditioning, rats
can encode the specific action-outcome relations to which they are
exposed during training. Furthermore, numerous findings suggest that,
in intact animals, instrumental performance is sensitive to the
contingency or causal relationship between performance of an action and
delivery of its specific outcome (Balleine and Dickinson, 1998a; Corbit
and Balleine, 2000).
With this in mind, one possible explanation of the low responding
observed in core-lesioned animals both in training and particularly after outcome devaluation in experiment 1 is that these lesions render
rats unable to encode specific action-outcome associations, and as
such, changes in the value of one outcome produced a general rather
than a selective reduction in lever-press performance on the test. This
possibility is examined in experiment 2.
Experiment 2: contingency degradation
The rats received sessions in which the contingency between one
action and its outcome on which they were trained was selectively degraded while the other action-outcome contingency remained intact [details of the procedure used have been reported elsewhere (Corbit and Balleine, 2000)]. After this training, the rats were given a test
in extinction on the two levers to assess the impact of the shift in
contingency. In agreement with previous findings, it was predicted that
sham animals should perform fewer responses on the lever for which the
action-outcome contingency has been degraded relative to the other
lever. If, however, the deficits observed in experiment 1 reflect an
impairment in the ability of core-lesioned rats to encode specific
action-outcome contingencies, then core-lesioned rats should fail to
show this effect; i.e., they should not show a selective decrease in
performance after degradation of one action-outcome contingency and
should perform both responses at comparable rates in the extinction test.
Contingency degradation training
The left panels of Figure
5 depict the effects of contingency
degradation training across days. ANOVA revealed a significant main
effect of group [F(2,21) = 6.107;
p < 0.01], suggesting that, as in experiment 1, rates
of responding differed between the three groups and suggesting an
effect of day [F(7,147) = 2.996;
p < 0.01] and, importantly, an effect of contingency
[F(1,21) = 9.117; p < 0.01] indicating that, overall, rats reduced responding on the
lever for which the contingency had been degraded. Furthermore, although a reliable day × contingency interaction emerged
[F(7,147) = 3.434; p < 0.01], indicating that the contingency effect increased across days
of training, no other interactions were significant (F < 1), confirming that a selective effect of contingency degradation emerged in each of the lesion groups. Importantly, although performance in the core-lesioned rats was lower than that in the sham- and shell-lesioned groups, they showed an effect of contingency degradation across days, an effect that persisted in the final extinction test
(Fig. 5, right panels). In general, therefore, it appears that all three groups were sensitive to degradation of the
action-outcome contingency and selectively reduced performance
accordingly.
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Figure 5.
Mean lever-press responses during tests of the
sensitivity of the animals to the selective degradation of one
instrumental action-outcome contingency in each of the lesioned
groups. A, Sham. B, Shell.
C, Core. For A-C, the left
panel displays mean lever presses per minute across days of
contingency degradation training, and the right panel
displays the mean responses per minute on the two levers in an
extinction test.
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Contingency extinction test
As indicated by the right panels of Figure 5, the
effect of contingency degradation found in training persisted in the
test conducted in extinction; i.e., the rats in each group performed fewer responses on the lever for which the instrumental contingency had
been degraded. ANOVA found a significant effect of group
[F(2,27) = 3.664; p < 0.05] and of contingency [F(1,21) = 20.661; p < 0.01], but, again, the group × contingency interaction was not reliable [F(2,21) = 1.123; p > 0.05]. This finding adds additional weight to the argument that,
although the overall rate of responding differed between the lesioned
groups, degradation of one instrumental contingency was effective in
each of the groups. As such, it is clear that neither core nor shell
lesions affected the ability of the rats to encode the specific
action-outcome associations to which they were exposed during
training. These data suggest that the effects of core lesions on the
devaluation tests in experiment 1 are unlikely to have been secondary
to a deficit in instrumental learning produced by the lesion.
Experiment 3: Pavlovian-instrumental transfer
The results of experiment 1 suggest that the instrumental
performance of animals with lesions of the NAC core is not sensitive to
selective devaluation of one outcome although the results of experiment
2 provide evidence that these same rats can encode the specific
action-outcome contingencies to which they were exposed during
training. Taken together, these results suggest that the NAC core,
although not involved in the process by which rats encode action-outcome associations, is critically involved in the process via
which the reward or incentive value of the instrumental outcome acts to
control instrumental performance.
Contrary to this view, it has occasionally been suggested that
outcome devaluation effects reflect a reduction in the excitatory effects of Pavlovian stimulus-outcome associations on instrumental performance (Rescorla and Solomon, 1967; Bindra, 1974, 1978). In
general, these two-process accounts suppose that, in the course of
instrumental training, stimuli that are present in the training situation become associated with the delivery of the instrumental outcome, and as a result of an excitatory relationship with reward, these stimuli can act to increase appetitive arousal, providing a
source of motivation capable of modulating instrumental performance. To
the extent that different cues predict different outcomes (e.g., the
sight of the lever or the sound of the pellet dispenser or the sucrose
pump), these stimulus-outcome associations could act to
modulate responding selectively and so, at least potentially, to
produce the differential performance observed in the outcome devaluation tests described in experiment 1. From this perspective, rather than affecting the impact of the incentive value of the instrumental outcome on performance, lesions of the NAC core may affect
instrumental performance by reducing the excitatory impact of Pavlovian cues.
In support of this suggestion, Pavlovian cues have been reported to
influence the performance of independently trained instrumental actions, and numerous studies have reported that, in hungry animals, the presentation of a stimulus paired previously with food in a
Pavlovian-conditioning phase can increase ongoing instrumental responding (Colwill and Rescorla, 1988; Balleine, 1994), an effect referred to as Pavlovian-instrumental transfer. In addition to having a
generally arousing impact on performance, it has also been shown that
specific cues can selectively enhance one but not another action
because of a shared outcome (Colwill and Motzkin, 1994). Results such
as these have been interpreted as suggesting that Pavlovian and
instrumental conditioning share a common reinforcement mechanism and,
hence, that Pavlovian and instrumental incentive processes are one and
the same (cf. for review, see Bindra, 1974, 1978).
Critical tests of this suggestion have proven difficult to devise, but
one prediction of relevance to the current study is that, on the basis
of the effect of core lesions on instrumental outcome devaluation in
experiment 1, lesions of the NAC core should also produce a deficit in
Pavlovian-instrumental transfer. As such, the purpose of experiment 3 was to examine whether the lesions that eliminated the specificity of
outcome devaluation in experiment 1 would also affect the ability of
Pavlovian cues to modulate instrumental performance in a
Pavlovian-instrumental transfer test similar to that used by
Colwill and Motzkin (1994).
In agreement with previous findings, we anticipated that the
sham-lesioned rats would show positive transfer such that in the
presence of a stimulus they would respond more on the lever that, in
training, delivered the same outcome that had been paired previously
with that stimulus during Pavlovian conditioning. If a common process
mediates transfer and outcome devaluation, then shell-lesioned rats
should be predicted to respond similarly to shams, whereas
core-lesioned rats should show little or no selective transfer on the test.
Pavlovian training
To assess whether animals learned about the relationship between
the stimuli and food presentations, the number of magazine entries
during the stimuli was compared with the number of entries in the
prestimulus interval. The training data are displayed in Figure
6, inspection of which suggests that
Pavlovian training was similar in the three groups. Preliminary
analysis suggested that there was no effect of stimulus type (noise vs
tone; F < 1), and so the data are presented collapsed
across stimulus. ANOVA revealed a significant effect of interval
(stimulus vs prestimulus) [F(1,20) = 127.3; p < 0.01], confirming that the rats made more magazine entries during the stimuli than in the prestimulus intervals, and a significant effect of training day
[F(7,140) = 8.765; p < 0.01], suggesting that as training proceeded the animals entered the magazine more during the stimuli. There was also a significant interval × day interaction
[F(7,140) = 4.690; p < 0.01], indicating that the difference between stimulus and
prestimulus intervals increased over days. There was, however, no
effect of group, and none of the interactions involving groups
approached significance (all F values < 1). There is
no evidence in this experiment, therefore, that the acquisition of
Pavlovian conditioning was affected by lesions of either the NAC core
or shell.
View larger version (13K):
[in this window]
[in a new window]
|
Figure 6.
Mean magazine entries per minute during CS
presentations and in the pre-CS interval across days of Pavlovian
training.
|
|
Pavlovian-instrumental transfer tests
The objective of this experiment was to assess the impact of
Pavlovian cues for reward on instrumental performance, and so for the
purpose of analysis, the number of lever presses during the baseline or
no-stimulus (Ø) period was subtracted from the number of lever presses
performed during each of the stimuli. Positive transfer is indicated,
using this measure, by positive numbers, whereas reduced transfer
should be reflected as numbers close to zero. The data from the
transfer tests are displayed in Figure
7.
View larger version (28K):
[in this window]
[in a new window]
|
Figure 7.
Mean lever presses per minute during the
presentation of each of the stimuli minus the mean lever presses per
minute during the no-stimulus (Ø) baseline period for each of the
three lesion groups. The term same refers to responding
during the stimulus that was paired with the same outcome as that
earned in training on that lever, whereas the term
different refers to responding during the stimulus that
was paired with a different outcome than that earned in training on
that lever.
|
|
It is clear from Figure 7 that a strong and selective positive transfer
effect emerged in both the sham- and core-lesioned groups with
responding on the lever that, in training, delivered the same outcome
signaled by the stimulus being elevated more than responding on the
other lever. In contrast, no positive transfer emerged in the
shell-lesioned group. The statistical analysis confirmed this
description; analysis of the test data revealed no effect of group
[F(2,20) = 2.568; p > 0.05] but did find a significant effect of stimulus (i.e., same vs
different) [F(1,2) = 13.379;
p < 0.01] and, critically, a significant
stimulus × group interaction
[F(2,20) = 6.257; p < 0.01]. Simple effects analyses revealed that, whereas there was a
significant effect of stimulus in both the sham-lesioned
[F(1,20) = 22.154; p < 0.01] and core-lesioned [F(1,20) = 3.288; p < 0.05] groups, there was no stimulus
effect in the shell-lesioned animals
[F(1,20) < 1].
These data strongly oppose the suggestion that outcome devaluation
effects can be explained in terms of the excitatory impact of Pavlovian
signals for reward on performance and suggest that the effects of core
lesions induced in experiment 1 were not produced by any deficit in
either Pavlovian conditioning or the excitatory impact of Pavlovian
cues on instrumental performance. This conclusion is further supported
by the striking deficit in transfer induced by shell lesions, a lesion
that was found in experiment 1 to have no impact whatever on the
sensitivity of the instrumental performance of the rat to the effects
of outcome devaluation.
| |
DISCUSSION |
The results of this series of studies have important implications
both for theories of accumbens function and, more generally, for
theories of instrumental conditioning. With respect to the latter, it
has long been argued that both primary incentives, such as foods and
fluids, and Pavlovian-conditioned stimuli that predict those incentives
affect instrumental performance via a common reward process (Rescorla
and Solomon, 1967; Bindra, 1974, 1978). In contrast to this position,
contemporary theories have drawn a strong distinction between these two
sources of reward arguing, instead, that the incentive value of the
instrumental outcome and the excitatory effects of Pavlovian cues on
instrumental performance are mediated by distinct learning processes
(Dickinson and Balleine, 1994; Balleine, 2000). The current results
provide strong evidence of this latter position. Thus, although sham- and shell-lesioned animals show a clear selective devaluation effect,
lesions localized to the accumbens core were found to eliminate the
ability of the incentive value of different outcomes to control
performance selectively after a specific satiety devaluation procedure.
Additionally, core lesions did not appear to affect the excitatory
influence of Pavlovian cues on instrumental performance. Together,
consideration of the pattern of behavior on all tests must point to a
specific deficit in the ability of the current value of different
outcomes to control performance selectively after lesions of the NAC core.
In contrast, lesions of the accumbens shell had no detectable effect on
outcome devaluation but had a clear and striking effect on the
excitatory influence of Pavlovian cues on instrumental performance,
eliminating the Pavlovian-instrumental transfer effect observed in
sham- and core-lesioned rats. As such, this study provides evidence
that instrumental and Pavlovian incentive learning processes are
independent and, furthermore, that these incentive processes
differentially involve accumbens core and shell, respectively.
A possible concern may be the somewhat depressed levels of responding
in core-lesioned animals observed in training. However, a comparison of
the performance of these animals on the last day of lever training and
their performance in the devaluation tests suggests that their behavior
on the test cannot be explained by a simple performance deficit. These
animals markedly decrease responding after the devaluation treatment
and additionally return to reasonable response levels in retraining
sessions, suggesting that it is the experimental manipulation rather
than a baseline effect that accounts for their low levels of
responding. Importantly, the same animals show normal sensitivity to
the degradation of one instrumental contingency despite their overall
lower levels of responding. This finding replicates the results of
Balleine and Killcross (1994) who also observed that lesions of the NAC depressed overall response rates while not having any effect on sensitivity to changes in the instrumental contingency. Balleine and
Killcross (1994) did not, however, observe any effects of their lesions
on performance after shifts in the motivational state of the animals,
suggesting intact incentive learning. However, the behavioral
procedures as well as the lesions were different in that study and may
not have been sensitive or selective enough to detect effects like
those observed in the current study. Further study will be required to
evaluate this apparent discrepancy properly.
The argument that accumbens core and shell mediate distinct functions
in instrumental conditioning is consistent with other recent theories
of accumbens function advanced on the basis of studies assessing the
intrinsic neuroanatomy and connectivity of the accumbens (Pennartz et
al., 1994; Wright and Groenewegen, 1995). Indeed, in recent reviews
Zahm (1999, 2000) has argued persuasively that core and shell regions
represent rather different forms of neural processing proposing the
existence of discrete neural networks involving these structures.
Although these networks are complex and their function is only
beginning to be understood, at least as applied to the neural
structures mediating instrumental conditioning, a degree of consensus
appears to be emerging. Thus, in agreement with the effects of core
lesions in the current study, the administration of AP-5 into the
accumbens core has been found to retard acquisition of the instrumental
response (Kelley et al., 1997). Additionally, administration of 6-OHDA
into the core has been shown to reduce instrumental performance
(Sokolowski and Salamone, 1998). Kelley and colleagues have argued that
this effect on the acquisition of the instrumental response after
administration of AP-5 implicates the accumbens core in instrumental
learning. Nevertheless, the finding in experiment 2 that, despite
reduced response levels, sensitivity to selective degradation of the
instrumental contingency remains primarily intact in core-lesioned rats
suggests otherwise. It appears that the acquisition of specific
action-outcome associations is mediated by structures afferent to the
accumbens but that, nevertheless, the core region plays a key role in
selecting or initiating actions based on the reward value of their
consequences. This view is similar to one recently advanced by
Sokolowski and Salamone (1998) and helps to clarify the source of the
lack of selectivity in outcome devaluation observed in experiment 1. Recall that, although only one of the two instrumental outcomes was
devalued in each of the extinction tests conducted in experiment 1, rats with lesions of the core, although manifestly sensitive to
devaluation per se, failed to distinguish in their performance between
the action that delivered the devalued outcome in training from the action that delivered previously the nondevalued outcome. Such a result
should be anticipated, however, if it is via the core region that the
current incentive value of the instrumental outcome acts to modulate performance.
In the current study lesions of the shell produced very different
effects on instrumental conditioning, having no effect on either
outcome devaluation or the selective degradation of the instrumental
contingency in experiments 1 and 2 but eliminating Pavlovian-instrumental transfer in experiment 3. Several previous reports have suggested that the shell region is responsive to signals
for reward (Johnson et al., 1995; Bassareo and DiChiara, 1997), and
indeed, lesions of the shell have been found to attenuate lever
pressing for stimuli paired previously with reward (Parkinson et al.,
1999). As such, these findings suggest that the shell region may
mediate the impact of stimulus-reward associations on instrumental
performance, a suggestion for which we found direct evidence in
experiment 3. After the pairings of two stimuli with either the pellet
or sucrose outcome used in instrumental training, the effect of these
stimuli on lever-press performance was assessed in a transfer test.
Both the sham- and the core-lesioned rats showed strong positive
transfer; i.e., the stimuli selectively elevated responding on the
lever that, in training, had delivered the same outcome that was
signaled by that stimulus. Importantly, this effect was not evident in
the shell-lesioned rats, suggesting that the lesion primarily abolished
the excitatory influence of Pavlovian stimuli on performance. This
effect does not appear to be because of a deficit in Pavlovian
conditioning in the shell-lesioned rats, nor, in view of their
performance in experiments 1 and 2, was it a consequence of their
inability to recall what outcome had been trained with the particular
action. Rather, it appears that it was the interaction of Pavlovian and
instrumental learning that was affected by the lesion.
The finding that lesions of the accumbens shell induce a deficit in
Pavlovian-instrumental transfer without affecting either Pavlovian or
instrumental conditioning per se suggests that the shell may be a
central structure through which feedback from cues associated with
reward helps to activate and guide actions that are instrumental to
gaining access to basic commodities. Again the work of Zahm (1999,
2000) is of interest in this context. This author notes that the
rich projections from the shell to the ventromedial pallidum appear to
provide the basis for feedback from the accumbens shell to cortical
structures thought to be involved in executive and premotor functions,
such as the prefrontal cortex, and to have strong projections back to
the core region of the accumbens. Because current evidence suggests
that the prelimbic region of the prefrontal cortex is strongly involved
in the formation of the instrumental action-outcome association
(Balleine and Dickinson, 1998a), this feedback loop would appear to
provide a ready means by which Pavlovian cues could affect instrumental
performance via the output of the core to other basal ganglia structures.
In summary, the current results provide evidence of a functional
dissociation in the involvement of the NAC core and shell in
instrumental conditioning and offer additional support for the
existence of two independent, interacting neural networks involving
these subregions. One network involving the core appears to be involved
in mediating the impact of evaluative processes via which animals
encode the incentive value of the instrumental outcome on the
performance of goal-directed actions. The second network, involving the
accumbens shell, appears to be involved in mediating the excitatory
effects of stimuli that anticipate reward on goal-directed performance.
| |
FOOTNOTES |
Received Nov. 17, 2000; revised Jan. 25, 2001; accepted Feb. 8, 2001.
This research was supported by the National Institute of Mental Health
Grant 56446 to B.W.B. We thank Sandra Cetl for her assistance with data collection.
Correspondence should be addressed to Laura Corbit, University of
California Los Angeles, Department of Psychology, Box 951563, Los
Angeles, CA 90095. E-mail: corbit{at}ucla.edu.
| |
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A. Nelson and S. Killcross
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P. J. Hernandez, M. E. Andrzejewski, K. Sadeghian, J. B. Panksepp, and A. E. Kelley
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D. Georgescu, R. M. Sears, J. D. Hommel, M. Barrot, C. A. Bolanos, D. J. Marsh, M. A. Bednarek, J. A. Bibb, E. Maratos-Flier, E. J. Nestler, et al.
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B. W. Balleine, A. S. Killcross, and A. Dickinson
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B. J. Everitt and M. E. Wolf
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P. Blundell, G. Hall, and S. Killcross
Lesions of the Basolateral Amygdala Disrupt Selective Aspects of Reinforcer Representation in Rats
J. Neurosci.,
November 15, 2001;
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[Abstract]
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TOP
ABSTRACT
INTRODUCTION
Compound via MeSH
