title: The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys.
abstract: Anandamide, an endogenous ligand for brain cannabinoid CB(1) receptors, produces many behavioral effects similar to those of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. Reinforcing effects of THC have been demonstrated in experimental animals, but there is only indirect evidence that endogenous cannabinoids such as anandamide participate in brain reward processes. We now show that anandamide serves as an effective reinforcer of drug-taking behavior when self-administered intravenously by squirrel monkeys. We also show that methanandamide, a synthetic long-lasting anandamide analog, similarly serves as a reinforcer of drug-taking behavior. Finally, we show that the reinforcing effects of both anandamide and methanandamide are blocked by pretreatment with the cannabinoid CB(1) receptor antagonist rimonabant (SR141716). These findings strongly suggest that release of endogenous cannabinoids is involved in brain reward processes and that activation of cannabinoid CB(1) receptors by anandamide could be part of the signaling of natural rewarding events.
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Justinova
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Tanda
authors.forename: Godfrey H
authors.initials: GH
authors.lastname: Redhi
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D063388:Endocannabinoids; D007262:Infusions, Intravenous; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D012054:Reinforcement, Psychology; D000077285:Rimonabant; D012453:Saimiri; D012646:Self Administration; D013237:Stereoisomerism; D019966:Substance-Related Disorders / Q000523:psychology
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; D003042:Cocaine; D000077285:Rimonabant; C078814:anandamide