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and glutamate immunolabeling within nerve terminals in the shell region of the nucleus accumbens were assessed in rats withdrawn from intravenous cocaine exposure. Four groups of rats were used: one group self-administered cocaine (0.42 mg/kg/infusion) in daily 3-h sessions for approximately 2 weeks, two additional groups received either saline or cocaine in a noncontingent fashion, and a fourth comprised a drug-naive, age-matched control group. Immunogold electron microscopy was used to quantify presynaptic terminal GABA and glutamate density within the vesicular and mitochondrial pools approximately 18 days following the last drug or saline exposure in the treatment groups. A significant 27.7% decrease in vesicular glutamate density within asymmetrical nerve terminals was observed in animals that self-administered cocaine as compared to controls. This group also showed an 18.6% decrease in vesicular nerve terminal glutamate immunolabeling as compared to animals that were administered a similar total dose of cocaine in a response-independent fashion. No significant changes in the density of nerve terminal GABA vesicular immunolabeling were observed in any groups. For both transmitters, no differences were detected in the density of immunolabeling within the presynaptic mitochondrial (i.e., metabolic) pool. These results demonstrate that glutamate density is suppressed in the shell region of the nucleus accumbens following withdrawal from 2 weeks of cocaine exposure. The findings also suggest that the motivational aspects that accompany self-administration may participate in this reduction.