A comparison of the discriminative stimulus effects of delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats

• Published in: Experimental and clinical psychopharmacology Vol. 12; no. 3; p. 173
• Main Authors: Wiley, Jenny L, LaVecchia, Kari L, Karp, Natalie E, Kulasegram, Sanjitha, Mahadevan, Anu, Razdan, Raj K, Martin, Billy R
• Format: Journal Article
• Language: English
• Published: United States 01.08.2004
• Subjects: Analgesics, Non-Narcotic - pharmacology; Analysis of Variance; Animals; Arachidonic Acids - chemistry; Arachidonic Acids - pharmacology; Behavior, Animal; Conditioning, Operant - drug effects; Discrimination (Psychology) - drug effects; Discrimination (Psychology) - physiology; Dose-Response Relationship, Drug; Dronabinol - pharmacology; Endocannabinoids; Male; Piperidines - pharmacology; Polyunsaturated Alkamides; Pyrazoles - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptors, Drug - agonists
• ISSN: 1064-1297; 1936-2293
• DOI: 10.1037/1064-1297.12.3.173

Efforts to determine whether Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and anandamide elicit similar discriminative stimulus effects have yielded conflicting results. The difficulty in establishing a discriminative cue to anandamide may be due to its metabolic instability. Rats were trained to discriminate either Delta(9)-THC or O-1812, a metabolically stable anandamide analog, from vehicle to avoid this issue. O-1812 and Delta(9)-THC substituted for each other; however, both drugs were more potent in the O-1812-trained rats. Further, O-1812 only substituted for Delta(9)-THC at response rate decreasing doses. The CB(1) antagonist, SR141716A, blocked the discriminative stimulus effects of both drugs but augmented their rate effects. O-1839, a VR(1) agonist, failed to substitute for either cannabinoid. These results suggest that the discriminative stimulus effects of Delta(9)-THC and O-1812 are similar, but subtle differences also exist.