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

Psychopharmacology (Berl). 1996 Oct;127(4):377-83. doi: 10.1007/s002130050101.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Drug Interactions
  • Excitatory Amino Acid Agonists / pharmacology*
  • Glutamates / pharmacology
  • Injections, Intraventricular
  • Male
  • Motor Activity / drug effects*
  • Narcotics / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*


  • Excitatory Amino Acid Agonists
  • Glutamates
  • Narcotics
  • 2,4-methanoglutamate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Cocaine