INHIBITORY EFFECTS OF DOPAMINE AND METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON GLUTAMATE-EVOKED FIRING OF NUCLEUS-ACCUMBENS AND CAUDATE-PUTAMENCELLS ARE ENHANCED FOLLOWING COCAINE SELF-ADMINISTRATION

Rats were allowed to self-administer cocaine during a 3-h session for 15 days. One to 11 days after the last cocaine exposure, rats were ane sthetized with urethane and effects of microiontophoretically-applied dopamine on glutamate-evoked firing of neurons in the nucleus accumben s and in the caudate/putamen were tested. Dopamine produced a dose-dep endent inhibition of glutamate-evoked firing in both the nucleus accum bens and the caudate/putamen of rats that had been repeatedly exposed to self-administered cocaine and in control rats. However, the DA-indu ced inhibition was significantly greater in the group that had self-ad ministered cocaine. The cocaine self-administration group was signific antly sensitized to the inhibitory effects of dopamine in both early ( 1-3 day) and later (9-11 days) periods of cocaine abstinence. Followin g cessation of repeated cocaine self-administration sessions, nucleus accumbens cells were also sensitized to the inhibitory effects of meth ylenedioxymethamphetamine (MDMA), a drug that increases extracellular levels of DA. and serotonin in the nucleus accumbens. This sensitizati on to DA- and MDMA-induced inhibition in the nucleus accumbens and in the striatum indicates that long-term neuroadaptations occur in these regions of the nervous system following repeated exposure to self-admi nistered cocaine.