Abstract
Interaction of cannabinoids with GABAergic systems has been noted in a number of previous studies. In the present study, this interaction was examined in a drug-discrimination paradigm. Rats were trained to discriminate either Δ 9-tetrahydrocannabinol (Δ 9-THC; 3 mg/kg) or diazepam (2.5 mg/kg) from vehicle in two-lever drug discrimination procedures for food reinforcement. As in previous studies, diazepam partially substituted for Δ 9-THC, but only at high doses that also decreased response rates. In contrast, Δ 9-THC did not substitute for diazepam in any of the rats. Hence, cross-generalization of these two drugs was asymmetrical. When tested in combination with diazepam, the brain cannabinoid (CB1) receptor antagonist SR141716A did not block the partial substitution of diazepam for Δ 9-THC, nor did it antagonize the discriminative stimulus effects of diazepam in diazepam-trained rats. These results suggest that the partial overlap in the discriminative stimulus effects of Δ 9-THC and diazepam is not mediated by diazepam action at CB1 receptors. However, the fact that diazepam produced partial substitution for Δ 9-THC is consistent with a GABAergic component to cannabinoid drug discrimination.
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