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J Neurophysiol 91: 314-323, 2004. First published October 1, 2003; doi:10.1152/jn.00638.2003
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Accumbal Neural Responses During the Initiation and Maintenance of Intravenous Cocaine Self-Administration

Laura L. Peoples1,2, Kevin G. Lynch3, Jamie Lesnock1 and Nidhi Gangadhar1

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

Submitted 3 July 2003; accepted in final form 26 September 2003

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

Address for reprint requests and other correspondence: L. L. Peoples, Department of Psychology, University of Pennsylvania, 3720 Walnut St., Philadelphia PA, 19104 (E-mail: lpeoples{at}psych.upenn.edu).




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