CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats

Behav Brain Res. 1999 Oct;104(1-2):141-6. doi: 10.1016/s0166-4328(99)00059-5.

Abstract

The effect of the CB1 cannabinoid receptor agonist WIN 55,212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55,212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB1 receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55,212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB1 cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Injections, Intravenous
  • Male
  • Morpholines / therapeutic use*
  • Naphthalenes / therapeutic use*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant
  • Self Administration

Substances

  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Cocaine
  • Rimonabant