Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from Δ9-tetrahyrocannabinol (Δ9-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received Δ9-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to Δ9-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic Δ9-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic Δ9-THC administration did not differ significantly. Tolerance to Δ9-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from Δ9-THC to a barbiturate that normally undergoes little metabolism.
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Chait, L.D., Brocco, M.J. & McMillan, D.E. Effects of chronic Δ9-tetrahyrocannabinol administration on schedule-controlled behavior of pigeons: Cross-tolerance to pentobarbital and barbital. Psychopharmacology 75, 1–4 (1981). https://doi.org/10.1007/BF00433491
- Schedule-controlled behavior