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.
Kokkinidis
L
L
Department of Psychology, University of Saskatchewan Saskatoon, Canada.
McCarter
B D
BD
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D012653:Self Stimulation / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000502:physiology; D013997:Time Factors
D003042:Cocaine