Background
Cocaine addiction is characterized by a progressive increase in drug intake and a
persistent craving for the drug during prolonged abstinence. Whether these two prominent
features of cocaine addiction are related to each other and are mediated by similar
or different neuronal processes is currently unknown.
Methods
Rats were first allowed to self-administer cocaine under long-access (6-hour) conditions
to induce escalation of cocaine intake. Self-administration sessions were designed
to measure both drug seeking and drug taking. After escalation, rats underwent a 1-month
period of forced abstinence after which they were re-exposed to cocaine to induce
re-escalation of cocaine intake. In vivo electrophysiologic recordings were conducted
in the core and shell subregions of the nucleus accumbens (NAc) during cocaine intake
escalation, after abstinence and during re-escalation.
Results
After abstinence, escalated levels of cocaine taking decreased toward pre-escalation
levels, whereas cocaine seeking increased persistently. These opposite postabstinence
changes were uncorrelated. At the neuronal level, the postabstinence decrease in cocaine
taking was correlated with a normalization of depressed neuronal activity in the NAc
shell that had developed during escalation of cocaine intake. In contrast, the incubation-like
increase in cocaine seeking was selectively correlated with a persistent increase
in the proportion of neurons in the NAc core that phasically fire during cocaine seeking.
Conclusions
These findings show that cocaine taking and cocaine seeking evolve differently during
abstinence from extended drug use and depend on dissociable neuronal processes in
different subregions of the nucleus accumbens.
Key Words
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Article info
Publication history
Published online: October 11, 2013
Accepted:
August 27,
2013
Received in revised form:
August 27,
2013
Received:
June 5,
2013
Footnotes
Authors SHA and LLP contributed equally to this work.
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
