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The Journal of Neuroscience, July 23, 2008, 28(30):7501-7512; doi:10.1523/JNEUROSCI.1071-08.2008

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Behavioral/Systems/Cognitive
Amphetamine Exposure Enhances Accumbal Responses to Reward-Predictive Stimuli in a Pavlovian Conditioned Approach Task

Xun Wan¹ and Laura L. Peoples^2,3

¹Department of Psychology, University of Pennsylvania, ²Department of Psychiatry, and ³Neuroscience Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Correspondence should be addressed to Dr. Laura L. Peoples, Department of Psychiatry, University of Pennsylvania School of Medicine, TRL Building, 125 South 31st Street, Philadelphia, PA 19104. Email: lpeoples{at}mail.med.upenn.edu

Acute and repeated exposure to psychostimulants such as amphetamine enhances the effects of pavlovian conditioned stimuli on conditioned behavior. It is hypothesized that amphetamine facilitates conditioned stimulus (CS) effects by selectively enhancing accumbal neuronal responses to stimuli. To test this hypothesis, rats were trained to discriminate between two pavlovian stimuli. One stimulus (i.e., CS+) was paired with sucrose delivery [i.e., unconditioned stimulus (US)], and the other stimulus (i.e., CS–) was paired with the absence of sucrose. Animals developed a conditioned approach response that occurred during the CS+ but not during the CS–. We tested the effect of different doses of amphetamine (0, 0.25, 0.5, or 1.0 mg/kg) on this conditioned approach behavior as well as on accumbal neuronal responses time locked to the CS+, the CS–, and the US. Acute amphetamine exposure increased conditioned approach behavior during the CS+, but not during the CS–. This change in behavior was associated with a selective increase in the magnitude of accumbal responses during the CS+. Repeated amphetamine administration followed by a drug-free period and reexposure did not affect the conditioned behavior, but increased accumbal responses to the CS+. These findings support the hypothesis that amphetamine exposure enhances behavioral responses to pavlovian conditioned stimuli by amplifying accumbal responses to those stimuli.

Key words: psychostimulant; dopamine; electrophysiology; addiction; learning; sensitization

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Received March 11, 2008; revised May 20, 2008; accepted June 4, 2008.

Correspondence should be addressed to Dr. Laura L. Peoples, Department of Psychiatry, University of Pennsylvania School of Medicine, TRL Building, 125 South 31st Street, Philadelphia, PA 19104. Email: lpeoples{at}mail.med.upenn.edu

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