Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice.
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.
Martellotta
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MC
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Cossu
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Fattore
L
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Gessa
G L
GL
Fratta
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D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D048588:Benzoxazines; D002186:Cannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D012201:Reward; D012646:Self Administration
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone