A comparison of the discriminative stimulus effects of delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats |
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Authors: | Wiley Jenny L LaVecchia Kari L Karp Natalie E Kulasegram Sanjitha Mahadevan Anu Razdan Raj K Martin Billy R |
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Affiliation: | Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 980613, USA. jwiley@hsc.vcu.edu |
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Abstract: | 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. |
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