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A comparison of the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats
Wiley, J., LaVecchia, KL., Karp, NE., Kulasegram, S., Mahadevan, A., Razdan, RK., & Martin, BR. (2004). A comparison of the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats. Experimental and Clinical Psychopharmacology, 12(3), 173-179. https://doi.org/10.1037/1064-1297.12.3.173
Efforts to determine whether Delta(9)-tetrahydrocannabmol (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, antagonist, SR141716A, blocked the discriminative stimulus effects of both drugs but augmented their rate effects. O-1839, a VR1 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