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

• Published in: Psychopharmacologia Vol. 156; no. 4; pp. 410 - 416
• Main Authors: FATTORE, Liana, COSSU, Gregorio, MARTELLOTTA, Cristina M, FRATTA, Walter
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.08.2001; Springer Nature B.V
• Subjects: Agonists; Analgesics - administration & dosage; Analgesics - pharmacology; Animals; Benzoxazines; Biological and medical sciences; Cannabinoid CB1 receptors; Cannabinoids - metabolism; Cannabis; Dose-Response Relationship, Drug; Drug abuse; Drug addictions; Drug delivery; Drug development; Drug dosages; Drug self-administration; Injections, Intravenous; Intravenous administration; Male; Medical sciences; Morpholines - administration & dosage; Morpholines - pharmacology; Naphthalenes - administration & dosage; Naphthalenes - pharmacology; Operant conditioning; Piperidines - pharmacology; Pyrazoles - pharmacology; Rats; Rats, Long-Evans; Receptors, Cannabinoid; Receptors, Drug - agonists; Receptors, Drug - antagonists & inhibitors; Reinforcement Schedule; Response rates; Rimonabant; Self Administration - psychology; Substance Abuse, Intravenous - psychology; Tetrahydrocannabinol; Toxicology; WIN 55,212-2; Animal model; Drug addiction; Agonist; Intravenous administration; Rat; Psychotropic; Rodentia; Instrumental conditioning; Self administration; Cannabinoid; Learning; Vertebrata; Mammalia; Acquisition process; Animal; Central nervous system disease; Drug of abuse; Antagonist; Reward; Biological receptor
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130100734

Delta9-tetrahydrocannabinol (Delta9-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. 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 microg/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. Response rate depended on the drug dose available, with maximum rates occurring at 12.5 microg/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. 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.