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The Journal of Neuroscience, March 15, 1999, 19(6):2401-2411
Dissociation in Effects of Lesions of the Nucleus Accumbens Core
and Shell on Appetitive Pavlovian Approach Behavior and the
Potentiation of Conditioned Reinforcement and Locomotor Activity by
D-Amphetamine
John A.
Parkinson1,
Mary C.
Olmstead2,
Lindsay
H.
Burns3,
Trevor W.
Robbins1, and
Barry J.
Everitt1
1 Department of Experimental Psychology, University of
Cambridge, Cambridge, United Kingdom CB2 3EB, 2 Department
of Psychology, Queens University, Kingston Ontario, Canada, K7L 3N6,
and 3 Neurex, Menlo Park, California, 94025-1012
Dopamine release within the nucleus accumbens (NAcc) has been
associated with both the rewarding and locomotor-stimulant effects of
abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After
excitotoxic lesions that selectively destroyed either the NAcc core or
shell, animals underwent additional CS-US training sessions and then
were tested for the acquisition of a new instrumental response that
produced the CS acting as a conditioned reinforcer (CR). Animals were
infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 µg) before each session. Shell lesions affected neither Pavlovian nor
instrumental conditioning but completely abolished the potentiative
effect of intra-NAcc amphetamine on responding with CR. Core-lesioned
animals were impaired during the Pavlovian retraining sessions but
showed no deficit in the acquisition of responding with CR. However,
the selectivity in stimulant-induced potentiation of the CR lever was
reduced, as intra-NAcc amphetamine infusions dose-dependently increased
responding on both the CR lever and a nonreinforced (control) lever.
Shell lesions produced hypoactivity and attenuated amphetamine-induced
activity. In contrast, core lesions resulted in hyperactivity and
enhanced the locomotor-stimulating effect of amphetamine. These results
indicate a functional dissociation of subregions of the NAcc; the shell
is a critical site for stimulant effects underlying the enhancement of
responding with CR and locomotion after intra-NAcc injections of
amphetamine, whereas the core is implicated in mechanisms underlying
the expression of CS-US associations.
Key words:
ventral striatum; reward; dopamine; psychomotor
stimulant; associative learning; drugs of abuse
Copyright © 1999 Society for Neuroscience 0270-6474/99/1962401-11$05.00/0
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