Initiation and Amplification 1 Accumbal neural responses during the initiation and maintenance of intravenous cocaine self- administration

During a chronic extracellular recording session, animals with a history of cocaine selfadministration 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. Neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug-free period were the only group that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. Like most accumbal neurons, a majority of the cells that were responsive during the drug-free period showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated at the onset of drug seeking 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 drugfree conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and drug-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.