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.
Bell
K
K
Department of VCAPP, Washington State University, Pullman 99164-6520, USA.
Kalivas
P W
PW
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D005971:Glutamates; D009294:Narcotics; C066302:2,4-methanoglutamate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D003042:Cocaine