Abstract
Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n=12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed ‘phasically active’) relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n=12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the ‘brain reward system’ following abstinence and resumption (relapse) of cocaine consumption.
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Acknowledgements
This research was supported by NIDA DA14339 to RMC and NIDA Training Grant DA07244 to JAH. We thank Yvette Peters and Robert Wheeler for helpful suggestions on the manuscript and Jay Elliott for help with data analysis.
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Hollander, J., Carelli, R. Abstinence from Cocaine Self-Administration Heightens Neural Encoding of Goal-Directed Behaviors in the Accumbens. Neuropsychopharmacol 30, 1464–1474 (2005). https://doi.org/10.1038/sj.npp.1300748
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DOI: https://doi.org/10.1038/sj.npp.1300748
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