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Psychopharmacology

, Volume 156, Issue 4, pp 410–416 | Cite as

Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats

  • Liana Fattore
  • Gregorio Cossu
  • Cristina M. Martellotta
  • Walter Fratta
Original Investigation

Abstract.

Rationale: Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A. Objective: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 µg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. Results: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 µg/kg per injection. Response rate increased following pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. Conclusion: Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.

Cannabinoid CB1 receptor WIN 55,212-2 Intravenous self-administration SR 141716A Rewarding properties Operant behaviour Rat 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Liana Fattore
    • 1
  • Gregorio Cossu
    • 2
  • Cristina M. Martellotta
    • 2
  • Walter Fratta
    • 1
  1. 1.B.B. Brodie Department of Neuroscience, University of Cagliari and Centre for Neuropharmacology, CNR, 09124 Cagliari, Italy
  2. 2.Neuroscience S.c.a.r.l., 09100 Cagliari, Italy

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