Binge self-administration and deprivation produces sensitization to the reinforcing effects of cocaine in rats.
BACKGROUND
Behavioral procedures that incorporate dynamic changes in drug-maintained behavior are needed to model the development of cocaine addiction in humans.


OBJECTIVE
Because sensitization may occur to some aspects of drug administration during the addiction process, the objective of the present study was to define the critical features of self-administration histories that result in subsequent increases in the reinforcing efficacy of cocaine (measured using the progressive ratio (PR) schedule).


METHODS
Animals were trained to self-administer cocaine on a fixed ratio (FR) schedule, baseline performance on a PR schedule was determined, and animals were given various histories of cocaine self-administration and drug deprivation. PR performance was reassessed following this experience.


RESULTS
Cocaine self-administration under a discrete-trials procedure (24 h/day) for 10 days, followed by a 7-day deprivation period resulted in sensitization to the reinforcing effects of cocaine as assessed by the PR schedule (increases in maximal breakpoints maintained by cocaine with no change in sensitivity at lower doses). Similar levels of daily cocaine intake on a FR schedule (typically completed within 6 h) coupled with a deprivation period failed to produce changes in breakpoint. Providing access to cocaine during the "deprivation period" by repeated testing on a PR schedule prevented the sensitization.


CONCLUSIONS
These data suggest that these self-administration-induced changes in breakpoint reflect sensitization, and show that a drug-free deprivation period is necessary, but not sufficient, to produce this increase.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. dmorgan@wfubmc.edu
Drake
D
Morgan
Mark A
MA
Smith
David C S
DC
Roberts
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000633:toxicity; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009042:Motivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D015819:Substance Abuse, Intravenous / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D003042:Cocaine