Postcocaine depression and sensitization of brain-stimulation reward: analysis of reinforcement and performance effects.

The effects of acute and chronic cocaine administration on intracranial self-stimulation (ICSS) were evaluated in a two-hole nose-poke discrimination paradigm. Analysis of ICSS rates as a function of current intensity revealed that cocaine increased rates of responding in a dose-dependent manner (5.0-20.0 mg/kg), resulted in a shift to the left of the rate-intensity function, and decreased thresholds for half-maximal responding. Brain-stimulation reward was modified by chronic exposure to cocaine, however, the direction of change was dependent on the schedule of drug administration. Repeated daily administration of cocaine (40.0 mg/kg) and ICSS testing 24 hr postinjection decreased rates and increased reward thresholds. A response depression was also observed when time-dependent variations in ICSS performance were evaluated after repeated cocaine administration. Using a different chronic cocaine/test schedule (30.0 mg/kg, twice daily), a sensitization of ICSS and decreased reward thresholds developed when rate-intensity functions were determined after 5-day drug intervals. These findings were discussed in terms of the role of dopamine in modulating central reward processes. It was suggested that depressed reward-system functioning might reflect reduced dopamine synthesis following cocaine withdrawal, and the ICSS sensitization was related to long-term compensatory changes in dopamine neurotransmission possibly involving presynpatic mechanisms.