Effects of SR141716A on diazepam substitution for delta9-tetrahydrocannabinol in rat drug discrimination

Pharmacol Biochem Behav. 1999 Nov;64(3):519-22. doi: 10.1016/s0091-3057(99)00130-6.


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 delta9-tetrahydrocannabinol (delta9-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 delta9-THC, but only at high doses that also decreased response rates. In contrast, delta9-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 delta9-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 delta9-THC and diazepam is not mediated by diazepam action at CB1 receptors. However, the fact that diazepam produced partial substitution for delta9-THC is consistent with a GABAergic component to cannabinoid drug discrimination.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoids / antagonists & inhibitors*
  • Diazepam / pharmacology*
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • GABA Modulators / pharmacology*
  • Generalization, Psychological / drug effects
  • Hallucinogens / pharmacology*
  • Male
  • Piperidines / pharmacology*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Rimonabant


  • Cannabinoids
  • GABA Modulators
  • Hallucinogens
  • Piperidines
  • Pyrazoles
  • Dronabinol
  • Diazepam
  • Rimonabant