Effects of chronic Δ⁹-tetrahyrocannabinol administration on schedule-controlled behavior of pigeons: Cross-tolerance to pentobarbital and barbital

Abstract

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.