Context-specific cross-sensitization between systemic cocaine and intra-accumbens AMPA infusion in the rat.

Two behavioral experiments were conducted in rats to evaluate the context-specificity of changes in nucleus accumbens glutamate transmission induced by systemic cocaine administration. At 2 weeks of withdrawal from daily cocaine injections (15 mg/kg, IP, daily x 7 days), subjects who had received cocaine in the test environment displayed a significantly greater motor response to intra-accumbens infusion of the glutamate receptor subtype-specific agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) than subjects who had received daily saline injections. Subjects who previously received cocaine in the home cage displayed no greater AMPA-induced motor activity within the test environment than saline-treated controls. In contrast, behavioral sensitization to an intra-accumbens challenge with the NMDA receptor-specific agonist, 1-aminocyclobutane-cis-1,3-dicarboxylic acid (cis-ACDA), was seen in both cocaine-treated subject groups. These results suggest that behavioral sensitization to psychostimulants may be mediated, in part, by a context-conditioned behavioral sensitization to glutamate transmission in the nucleus accumbens through AMPA/kainate receptors.