REDUCED GLUTAMATE IMMUNOLABELING IN THE NUCLEUS-ACCUMBENS FOLLOWING EXTENDED WITHDRAWAL FROM SELF-ADMINISTERED COCAINE

Alterations in the density of GABA and glutamate immunolabeling within nerve terminals in the shell region of the nucleus accumbens were ass essed in rats withdrawn from intravenous cocaine exposure. Four groups of rats were used: one group self-administered cocaine (0.42 mg/kg/in fusion) in daily 3-h sessions for approximately 2 weeks, two additiona l groups received either saline or cocaine in a noncontingent fashion, and a fourth comprised a drug-naive, age-matched control group. Immun ogold electron microscopy was used to quantify presynaptic terminal GA BA and glutamate density within the vesicular and mitochondrial pools approximately 18 days following the last drug or saline exposure in th e treatment groups. A significant 27.7% decrease in vesicular glutamat e density within asymmetrical nerve terminals was observed in animals that self-administered cocaine as compared to controls. This group als o showed an 18.6% decrease in vesicular nerve terminal glutamate immun olabeling as compared to animals that were administered a similar tota l dose of cocaine in a response-independent fashion. No significant ch anges in the density of nerve terminal GABA vesicular immunolabeling w ere observed in any groups. For both transmitters, no differences were detected in the density of immunolabeling within the presynaptic mito chondrial(i.e., metabolic) pool. These results demonstrate that glutam ate density is suppressed in the shell region of the nucleus accumbens following withdrawal from 2 weeks of cocaine exposure. The findings a lso suggest that the motivational aspects that accompany self-administ ration may participate in this reduction. (C) 1998 Wiley-Liss, Inc.