Time course of changes in cocaine self-administration behavior in rats during immunization with the cocaine vaccine IPC-1010
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Rationale: Following a 6-week immunization period consisting of three biweekly injections of the cocaine vaccine IPC-1010, the reacquisition of cocaine self-administration behavior in rats was previously shown to be reduced in a manner that was dependant on serum antibody level. The present studies were conducted to examine additional issues relevant to the clinical use of the vaccine. Objectives: One experiment was conducted to address the issue of whether exposure to cocaine during the immunization period would influence the ability of the vaccine to block cocaine self-administration. A second experiment was conducted to determine if the reductions in drug-seeking behavior and drug intake by the vaccine were behaviorally specific, or if behavior maintained by a non-drug reinforcer would be similarly affected. Methods: Identical second-order schedules of cocaine (1 mg/kg) or food pellet (45 mg) delivery were used in rats. In both studies, the time course of changes in behavior during the 6-week immunization period was examined in vaccine and alum-treated control rats following baseline and extinction conditions. Results: The cocaine vaccine IPC-1010 induced average serum antibody levels of 0.07 mg/ml and significantly reduced self-administration behavior during the 2-week period following the third vaccine boost in a subgroup of rats with serum antibody levels greater than the average value. Cocaine self-administration behavior at this time point significantly correlated with serum antibody level. IPC-1010 did not alter responding maintained by food throughout the immunization period although serum antibody levels reached a similar average of 0.06 mg/ml in this group of rats. Conclusions: These findings suggest that the reductions in drug-seeking behavior and drug intake after immunization with IPC-1010 did not result from a reduced ability of the rats to respond on the lever. Furthermore, daily exposure to cocaine during the immunization period did not influence the ability of the vaccine to reduce cocaine self-administration behavior that emerged gradually over time. These findings also confirm the need for a sufficiently high antibody level to blunt the reinforcing effects of cocaine.
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