Effects of SR141716A on diazepam substitution for delta9-tetrahydrocannabinol in rat drug discrimination.
Pharmacology, Biochemistry, and Behavior November 1999 DOI: 10.1016/s0091-3057(99)00130-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug-discrimination study in rats Peer reviewed |
|---|---|
| Population | Rats trained to discriminate delta9-THC or diazepam from vehicle |
| Interventions | diazepam SR141716A |
| Dose | delta9-THC 3 mg/kg; diazepam 2.5 mg/kg |
| Topics | Cannabis |
| Key points | Diazepam partially substituted for delta9-THC only at high doses that also decreased response rates, while delta9-THC did not substitute for diazepam, indicating asymmetrical cross-generalization. The CB1 antagonist SR141716A did not block diazepam's partial substitution or its discriminative effects, suggesting this overlap is not mediated by CB1 receptors, though the authors note it is consistent with a GABAergic component to cannabinoid discrimination. |
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 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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 7
- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
- Effects of ketamine enantiomers on morphine and THC subjective effects in rats. Journal of Psychopharmacology December 26, 2025
- Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs. Current Topics in Behavioral Neurosciences 2018
- Discriminative Stimulus Properties of the Endocannabinoid Catabolic Enzyme Inhibitor SA-57 in Mice. Journal of Pharmacology and Experimental Therapeutics August 2016
- Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug and Alcohol Dependence October 1, 2014
and 2 more in the library
Cites 3
- Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of pigeons and rats. Psychopharmacology April 1996
- Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats. Neuropharmacology June 1995
- Pharmacological specificity of delta 9-tetrahydrocannabinol discrimination in rats. Psychopharmacology April 1995