Effects of SR141716A on diazepam substitution for Delta(9)-tetrahydrocannabinol in rat drug discrimination
Wiley, J., & Martin, B. R. (1999). Effects of SR141716A on diazepam substitution for Delta(9)-tetrahydrocannabinol in rat drug discrimination. Pharmacology, Biochemistry, and Behavior, 64(3), 519-522.
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 Delta(9)-tetrahydrocannabinol (Delta(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 Delta(9)-THC, but only at high doses that also decreased response rates. In contrast, Delta(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 Delta(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 Delta(9)-THC and diazepam is not mediated by diazepam action at CBI receptors. However, the fact that diazepam produced partial substitution for Delta(9)-THC is consistent with a GABAergic component to cannabinoid drug discrimination. (C) 1999 Elsevier Science Inc