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.
A FORTRAN 77 program is presented which computes the Rao (1970) global test and the subsequent Levy (1976) multiple range procedure for testing the differences among independent correlations.
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