Psychopharmacology

, Volume 144, Issue 2, pp 144–150 | Cite as

Blockade of cannabinoid (CB1) receptors by SR 141716 selectively antagonizes drug-induced reinstatement of exploratory behaviour in gerbils

  • M. Poncelet
  • Marie-Christine Barnouin
  • Jean-Claude Brelière
  • Gérard Le Fur
  • Philippe Soubrié
Original Investigation

Abstract

Rationale: A cannabinoid hypothesis of schi- zophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system. Objective: The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms. Methods: Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor. Results: SR 141716 (0.3–3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils. Conclusion: The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.

Key words Cannabinoid receptor Locomotor activity Habituation Antipsychotic drug Gerbils 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • M. Poncelet
    • 1
  • Marie-Christine Barnouin
    • 1
  • Jean-Claude Brelière
    • 1
  • Gérard Le Fur
    • 1
  • Philippe Soubrié
    • 1
  1. 1.Sanofi Recherche, Rue Pr J. Blayac, F-34184 Montpellier Cedex 04, France e-mail: martine.poncelet@sanofi.com, Fax: +33-4-67-10-69-12FR

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