1. ¹Department of Psychology, The University of Chicago, Chicago, IL, USA
2. ²Department of Psychiatry, The University of Chicago, Chicago, IL, USA

Correspondence: P Vezina, Department of Psychiatry, The University of Chicago, 5841 S. Maryland Avenue, MC 3077, Chicago, IL 60637, USA. Tel: +1 773 702 2890; Fax: +1 773 702 0857; E-mail: pvezina@yoda.bsd.uchicago.edu

Received 2 July 2002; Revised 13 September 2002; Accepted 19 September 2002.

Abstract

Previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) enhances cocaine self-administration in a D₁ dopamine receptor-dependent manner. The present study examined the contribution of VTA NMDA, AMPA/kainate, and metabotropic glutamate (mGlu) receptors to this effect. Rats in different groups received three intra-VTA injections, one every third day, of either saline (0.5 l/side), AMPH (2.5 g/0.5 l/side), AMPH+CPP (NMDA receptor antagonist; 10 M or 100 M/0.5 l/side), AMPH+CNQX (AMPA/kainate receptor antagonist; 0.3 mM or 1 mM/0.5 l/side), AMPH+MCPG (mGlu receptor antagonist; 0.5 mM or 50 mM/0.5 l/side), or the glutamate receptor antagonists alone. Starting 7–10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) and then tested under a progressive ratio (PR) schedule of reinforcement for 6 consecutive days. As reported previously, VTA AMPH pre-exposed rats worked more and obtained more infusions of cocaine than saline pre-exposed animals. Coadministration of CPP, CNQX, or MCPG with AMPH during pre-exposure dose-dependently blocked this enhancement of cocaine self-administration. Rats pre-exposed to the glutamate receptor antagonists alone did not differ on the test days from the saline pre-exposed controls. These results indicate that, in a manner paralleling the induction of sensitization of the locomotor stimulating effects of AMPH, activation of NMDA, AMPA/kainate, and mGlu receptors during pre-exposure to AMPH in the VTA is necessary for the enhancement of cocaine self-administration to develop.