Neurophysiological effects of cocaine abstinence

2006 2006

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Abstract (summary)

Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking behavior and resumption of drug consumption (relapse). Numerous studies have implicated the brain 'reward' circuit, including the nucleus accumbens (Acb) and associated brain regions, in mediating drug-seeking behaviors. Using electrophysiological recording procedures in behaving rodents, we have shown that Acb neurons encode information about key aspects of goal-directed behaviors. Moreover, we have shown that cell firing in this region is sensitive to interruption (extinction) of response-reinforcement contingencies involving drug or natural rewards. To extend these findings to a more clinically relevant model, electrophysiological recording procedures were used here to determine the firing properties of Acb neurons following abstinence (i.e., experimenter-controlled removal of drug access) from cocaine self-administration.

Experiments in Chapter 2 revealed that the percentage of Acb cells that encode cocaine-seeking behavior is dramatically increased during resumption of cocaine self-administration following 1-month cocaine abstinence. Extinction experiments in another set of rats revealed an increased motivational state for the drug following 1-month abstinence.

Studies in Chapter 3 showed that these effects were also observed in animals that underwent extended (2-month) abstinence from cocaine self-administration. Since there were possible confounding variables such as increased age and extended time of microwire implantation for the 2-month group, appropriate controls were included in this experiment.

The ability of cocaine-associated stimuli to elicit drug-seeking even after years of abstinence is problematic for addicts who wish to remain drug-free. In Chapter 4 we show that activation of Acb neurons by cocaine-associated stimuli was enhanced following 1-month cocaine abstinence regardless of contingency of cue presentation or cocaine availability.

Taken together, our results show that 1- and 2-month abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information (Chapters 2 & 3), and that Acb neurons are more responsive to cocaine-associated cues following 1-month abstinence across multiple environmental contexts (Chapter 4). Overall, the present report highlights cellular changes in the Acb following cocaine abstinence that may represent one type of neuroadapation related to cocaine taking and abstinence from drug use underlying the inability of cocaine addicts to remain drug free.

Indexing (details)

Physiological psychology;
0989: Physiological psychology
0623: Psychology
0623: Experiments
0349: Psychobiology
Identifier / keyword
Psychology; Cocaine abstinence; Electrophysiology; Neurophysiological; Withdrawal
Neurophysiological effects of cocaine abstinence
Hollander, Jonathan Alan
Number of pages
Publication year
Degree date
School code
DAI-B 67/06, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Carelli, Regina M.
The University of North Carolina at Chapel Hill
University location
United States -- North Carolina
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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