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Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in an NMDA, AMPA/kainate, and metabotropic glutamate receptor-dependent manner

Academic Article
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Overview

authors

  • Suto, Nobuyoshi
  • Tanabe, L. M.
  • Austin, J. D.
  • Creekmore, E.
  • Vezina, P.

publication date

  • April 2003

journal

  • Neuropsychopharmacology  Journal

abstract

  • Previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) enhances cocaine self-administration in a D(1) 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 microl/side), AMPH (2.5 microg/0.5 microl/side), AMPH+CPP (NMDA receptor antagonist; 10 microM or 100 microM/0.5 microl/side), AMPH+CNQX (AMPA/kainate receptor antagonist; 0.3 mM or 1 mM/0.5 microl/side), AMPH+MCPG (mGlu receptor antagonist; 0.5 mM or 50 mM/0.5 microl/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.

subject areas

  • Amphetamine
  • Animals
  • Cocaine
  • Male
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Reinforcement Schedule
  • Self Administration
  • Ventral Tegmental Area
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Research

keywords

  • amphetamine
  • cocaine
  • cross-sensitization
  • glutamate receptors
  • self-administration
  • ventral tegmental area
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Identity

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/sj.npp.1300075

PubMed ID

  • 12655307
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Additional Document Info

start page

  • 629

end page

  • 639

volume

  • 28

issue

  • 4

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