Antagonism of ∆⁹-THC induced behavioral effects by rimonabant: time course studies in rats.
Torbjörn U C Järbe, Roger S Gifford, Alexandros Makriyannis
European Journal of Pharmacology December 1, 2010 DOI: 10.1016/j.ejphar.2010.09.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal behavioral pharmacology study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Rimonabant |
| Dose | Rimonabant 1 mg/kg; THC training doses 1.8 and 3 mg/kg |
| Duration | Tests at 20, 60, 120, and 240 minutes after rimonabant administration; THC given 20 minutes before testing |
| Topics | Cannabis |
| Key points | Rimonabant at 1 mg/kg antagonized the discriminative stimulus and response-suppressing effects of delta-9-THC in rats, but the antagonism was short lived. Estimated functional half-lives were 128.4 and 98.4 minutes in the two drug-discrimination groups and 118.9 minutes in the fixed-ratio responding procedure. |
Abstract
The objective was to examine the time course of the cannabinoid 1 receptor antagonist/inverse agonist rimonabant's ability to antagonize in vivo cannabinergic agonist effects. We used two behavioral procedures sensitive to the effects of ∆⁹-tetrahydrocannabinol (∆⁹-THC): rat drug discrimination (EXP-1) and suppression of fixed-ratio responding (FR) for food reinforcement (EXP-2). Two training doses of ∆⁹-THC (1.8 and 3 mg/kg) served as discriminative cues in two groups discriminating ∆⁹-THC from vehicle; injections were i.p. 20 min before session onset. Tests assessed the dose-response functions of ∆⁹-THC and the time course for rimonabant in its ability to block the discriminative stimulus effects of ∆⁹-THC. For antagonism testing, the training doses of ∆⁹-THC were used and the rimonabant dose was 1mg/kg. Tests were 20, 60, 120, and 240 min post rimonabant administration; ∆⁹-THC was always administered 20 min prior to testing. For EXP-2, only one response lever was activated and every 10th (FR-10) press on that lever resulted in food delivery. Once the response rate stabilized, tests occurred with ∆⁹-THC, rimonabant and combinations of the drugs. The ED(50) estimates for the dose-response functions were 0.38 (±0.28-0.51) and 0.50 (±0.40-0.63) mg/kg for the training doses of 1.8 and 3 mg/kg ∆⁹-THC, respectively. The time course studies suggested functional half-life estimates of 128.4 (±95.7-172.2) and 98.4 (±64.2-150.7) min by rimonabant for the two groups in EXP-1, respectively. Similarly, the functional half-life of rimonabant was 118.9 (±66.1-213.9) min in EXP-2. Thus, antagonism of ∆⁹-THC by rimonabant is relatively short lasting.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Effects of ketamine enantiomers on morphine and THC subjective effects in rats. Journal of Psychopharmacology December 26, 2025
- A critical assessment of the abuse, dependence and associated safety risks of naturally occurring and synthetic cannabinoids. Frontiers in Psychiatry 2024
- Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs. Current Topics in Behavioral Neurosciences 2018
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