Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice

Neuroscience. 1998 Jul;85(2):327-30. doi: 10.1016/s0306-4522(98)00052-9.


Marijuana is one of the most widely used illicit recreational drugs. However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased. The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Animals
  • Avoidance Learning / drug effects
  • Benzoxazines
  • Cannabinoids / agonists
  • Cannabinoids / antagonists & inhibitors
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morpholines / administration & dosage*
  • Naphthalenes / administration & dosage*
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Reward
  • Self Administration


  • Analgesics
  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • 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