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

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from Δ-tetrahyrocannabinol (Δ-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received Δ-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to Δ-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic Δ-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 Δ-THC administration did not differ significantly. Tolerance to Δ-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 Δ-THC to a barbiturate that normally undergoes little metabolism. [ABSTRACT FROM AUTHOR]