Evidence for sensitization of cocaine-induced nucleus accumbens glutamate release.

Cocaine-stimulated glutamate release in the nucleus accumbens was studied following chronic cocaine or saline pretreatment in order to determine whether this effect was sensitized in rats showing augmented dopamine release, locomotor and stereotypy responses. Rats were pretreated with cocaine (30 mg kg-1) or saline for 5 consecutive days and were tested with cocaine (15 mg kg-1) after a 10-day withdrawal period. Cocaine-induced glutamate release, dopamine release, horizontal locomotor activity and stereotypy were monitored simultaneously in animals undergoing in vivo microdialysis in the nucleus accumbens. The basal levels of extracellular glutamate and dopamine, as well as locomotor activity, were not different between cocaine- and saline-pretreated groups. Following cocaine injection the increase in glutamate release, dopamine release, locomotor activity and stereotypy were greater in the cocaine-pretreated animals. These results show that cocaine-stimulated glutamate release in the nucleus accumbens is sensitized following chronic cocaine pretreatment.