REPEATED COCAINE ADMINISTRATION ALTERS EXTRACELLULAR GLUTAMATE IN THEVENTRAL TEGMENTAL AREA

The present study determined if repeated cocaine injections alter the effect of cocaine on extracellular glutamate in the ventral tegmen tal area (VTA). All rats were treated with daily cocaine (15 mg/kg i.p. x 2 days, 30 mg/kg i.p. x 5 days) or saline for 7 days. At 21 days afte r discontinuing the daily injections, a dialysis probe was placed into the VTA and the extracellular levels of glutamate were estimated. A s ystemic injection of cocaine (15 mg/kg i.p.) elevated extracellular gl utamate in the VTA of rats pretreated with daily cocaine but not in th e daily saline-pretreated subjects. No significant change in glutamate was produced by a saline injection in either pretreatment group. In a group of rats pretreated with daily cocaine, the D-1 antagonist SCH-2 3390 (30 mu M) was infused through the dialysis probe prior to the acu te injections of saline and cocaine. SCH-23390 prevented the increase in extracellular glutamate associated with the acute administration of cocaine. Behavioral data were collected simultaneously with the measu res of extracellular glutamate. The behavioral stimulant effect of coc aine was greater in cocaine-pretreated than saline-pretreated subjects , and the behavioral augmentation in cocaine-pretreated rats was partl y blocked by SCH-23390. These data support the hypotheses that repeate d cocaine administration produces an increase in the capacity of D-1 r eceptor stimulation to release glutamate in the VTA and that this mech anism partly mediates behavioral sensitization produced in rats treate d with daily cocaine injections.