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

• Published in: Neuroscience Vol. 85; no. 2; pp. 327 - 330
• Main Authors: Martellotta, M.C., Cossu, G., Fattore, L., Gessa, G.L., Fratta, W.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.1998; Elsevier
• Subjects: Analgesics - administration & dosage; Animals; Avoidance Learning - drug effects; Behavioral psychophysiology; Benzoxazines; Biological and medical sciences; cannabinoid receptor CB 1; Cannabinoids - agonists; Cannabinoids - antagonists & inhibitors; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred Strains; Morpholines - administration & dosage; Naphthalenes - administration & dosage; Neurotransmission and behavior; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Cannabinoid; Receptors, Drug - agonists; Reward; Self Administration; SR 141716A; WIN 55,212-2; reward; self-administration; SR 141716A; CB 1, brain cannabinoid receptor-1; WIN 55,212-2; cannabinoid receptor CB 1; mice; R, reward index; NPR, nose-poke response; Δ 9-THC, Δ 9-tetrahydrocannabinol; Vertebrata; Agonist; Mammalia; Mouse; Animal; Rodentia; Self administration; Reward; Cannabinoid; Biological receptor
• ISSN: 0306-4522; 1873-7544
• 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 CB 1 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 CB 1 receptors.