The role of benzodiazepine receptors in the discriminative stimulus properties of delta-9-tetrahydrocannabinol.
D J Mokler, B D Nelson, L S Harris, J A Rosecrans
Life Sciences April 28, 1986 DOI: 10.1016/0024-3205(86)90497-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal behavioral pharmacology experiment (drug discrimination study) Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Male Sprague-Dawley rats trained to discriminate 3.0 mg/kg THC from vehicle |
| Interventions | delta-9-tetrahydrocannabinol (THC) Diazepam Pentobarbital Ro 15-1788 |
| Dose | 3.0 mg/kg THC; diazepam 0.1 to 10.0 mg/kg; Ro 15-1788 2.0 mg/kg; pentobarbital 1 to 10 mg/kg |
| Topics | Cannabis |
| Key findings | Thirteen of 20 rats generalized from THC to diazepam in a dose-dependent manner (0.1–10.0 mg/kg), while seven showed no generalization at any dose. The benzodiazepine antagonist Ro 15-1788 blocked this generalization in the first group but increased THC lever responding in the second. The authors suggest THC's discriminative stimulus properties share some commonality with diazepam's effects in a subpopulation of rats, probably mediated by benzodiazepine receptors. |
Abstract
Twenty male Sprague-Dawley rats were trained to discriminate 3.0 mg/kg delta-9-tetrahydrocannabinol (THC) from its vehicle. Following acquisition of this discrimination animals were tested for generalization to 3.0 mg/kg diazepam. Thirteen animals showed a generalization from THC to diazepam, whereas the remaining seven animals did not. The generalization curve for diazepam was dose-dependent from 0.1 to 10.0 mg/kg in the first group; the latter group showed no generalization from THC at any dose of diazepam in this range. No differences were found between these groups in the generalization curve for THC. The benzodiazepine antagonist Ro 15-1788 (2.0 mg/kg) antagonized the generalization to diazepam in the group that discriminated diazepam as THC. In contrast, Ro 15-1788 increased THC lever responding of 10 mg/kg diazepam in the group which did not generalize from THC. Ro 15-1788 did not alter the discriminability of THC in either group. THC also showed partial generalization to pentobarbital (1 to 10 mg/kg). The generalization was again complete in one subgroup and absent in another, but there was only a 43 percent overlap between the subgroups found with testing for generalization to diazepam. The percent THC lever responding with 3.0 mg/kg pentobarbital was increased by Ro 15-1788 in the group which generalized to diazepam, but not the other group. These data suggest that the discriminative stimulus properties of THC may have some commonality with the effects of diazepam in a subpopulation of rats trained to discriminate THC. These THC-like effects of diazepam are probably mediated by benzodiazepine receptors since they are antagonized by a specific benzodiazepine receptor antagonist.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 9
- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
- Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs. Current Topics in Behavioral Neurosciences 2018
- 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
- Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). Pharmacology, Biochemistry, and Behavior July 2014
- Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol. Psychopharmacology April 2009
and 4 more in the library