(R)-methanandamide, but not anandamide, substitutes for delta 9-THC in a drug-discrimination procedure.
Fourteen male rats were trained to discriminate between injections of 2 mg/kg delta-9-tetrahydrocannabinol (delta 9-THC) and vehicle in a 2-lever operant drug-discrimination paradigm. Following training, substitution tests using a cumulative dosing procedure revealed that anandamide (0.5-16 mg/kg ip), the putative endogenous camabinoid receptor ligand, failed to generalize to the discriminative stimulus properties of the training dose of delta 9-THC. However, dose-dependent generalization to the delta 9-THC cue was observed following administration of both CP-55,940 (0.05-0.8 mg/kg ip), a synthetic cannabinoid, and (R)-methanandamide (0.5-8 mg/kg ip), a metabolically stable analog of anandamide. Collectively, these results demonstrate a cannabinoid-specific in vivo effect of an anandamide compound and suggest that the naturally occurring form of anandamide may be metabolized too rapidly to produce a cannabimimetic intercceptive state when administered peripherally.
Burkey
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RT
Department of Psychology, Texas A&M University, USA. rtburkey@ehc.edu
Nation
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JR
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D005795:Generalization, Stimulus / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley
D001095:Arachidonic Acids; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D006213:Hallucinogens; D053284:Polyunsaturated Alkamides; C088155:methanandamide; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C078814:anandamide