Orally delivered cocaine functions as a positive reinforcer in C57BL/6J mice

Cocaine serves as a reinforcer across several routes of administration and species. However, whether orally delivered cocaine serves as a positive reinforcer has not been systematically established. We determined the extent to which contingent access to orally delivered cocaine would maintain lever pressing behavior in C57BL/6J mice who had a prior history of operant ethanol-reinforced behavior. The findings presented in this report demonstrate that orally delivered cocaine can serve as a reinforcer of operant behavior. A drug substitution procedure where cocaine was substituted for gradually decreasing ethanol concentrations was successful in inducing pharmacologically significant intakes of cocaine under a fixed ratio (FR) schedule of drug access. When ethanol was removed, responding for cocaine continued. As FR size was increased, proportionate increases in responding occurred except at the highest FR value. Responding maintained by cocaine significantly exceeded responding maintained by vehicle, with the mice typically consuming 6-10 mg/kg cocaine per 30-min session. The utilization of inbred strains and the procedures followed in the present studies should prove useful in determining the extent of both genetic and environmental influences on various behavioral effects of cocaine and their mechanisms of action.