(R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide.
Torbjörn U C Järbe, R J Lamb, S Lin, Alexandros Makriyannis
Psychopharmacology August 2001 DOI: 10.1007/s002130100730 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Peer reviewed |
|---|---|
| Population | Rats trained in a two-lever operant drug discrimination procedure |
| Interventions | (R)-methanandamide (AM-356) Delta9-THC SR-141716 anandamide |
| Dose | 10 mg/kg (R)-methanandamide; 3, 1.8, and 5.6 mg/kg Delta9-THC; 0.3 and 1 mg/kg SR-141716; 10 and 18 mg/kg anandamide; 1 and 10 mg/kg SR-141716 alone |
| Duration | Pretreatment times of 3, 15, and 30 minutes; effects tested up to 1 hour after (R)-methanandamide |
| Topics | Cannabis |
| Key points | Delta9-THC was more potent than (R)-methanandamide in producing discriminative stimulus effects in rats, and the CB1 antagonist SR-141716 blocked these effects, with surmountable antagonism only at 0.3 mg/kg in (R)-methanandamide-trained rats. Anandamide substituted for (R)-methanandamide only at a short (3-minute) pretreatment time and produced little Delta9-THC-appropriate responding. The authors argue the results indicate both similarities and dissimilarities between classical cannabinoids such as THC and endogenous fatty acid ethanolamides. |
Abstract
(R)-methanandamide (AM-356), a metabolically more stable chiral analog of the endocannabinoid ligand anandamide, was used as a representative of fatty acid ethanolamide CB1 receptor ligands to characterize the discriminative stimulus functions of anandamides. Rats discriminated between 10 mg/kg (R)-methanandamide and vehicle administered IP 15 min prior to session onset. Another group of rats was initially trained to discriminate between 3 mg/kg Delta9-THC and vehicle given IP 30 min prior to session onset; for anandamide testing, the animals were retrained with 1.8 and 5.6 mg/kg Delta9-THC. A two lever operant methodology (FR10) was used. Delta9-THC was more potent than (R)-methanandamide at both 15 and 30 min post-injection, irrespective of the training drug used. Additional tests with 10 and 18 mg/kg (R)-methanandamide suggested that the effects were declining by 1 h. The cannabinoid antagonist SR 141716 (0.3 and 1 mg/kg) produced rightward shifts in the Delta9-THC dose-response curve for Delta9-THC-appropriate responding and for (R)-methanandamide-appropriate responding (surmountable antagonism). SR-141716 (0.3 and 1 mg/kg) antagonized the ability of (R)-methanandamide to occasion either Delta9-THC-appropriate responding or (R)-methanandamide-appropriate responding. This antagonism was surmountable only at a dose of 0.3 mg/kg SR-1421716 in the (R)-methanandamide-trained rats. SR-141716 did not antagonize the rate-decreasing effects of (R)-methanandamide in either the Delta9-THC or the (R)-methanandamide trained rats. Response suppression precluded testing doses higher than 30 mg/kg (R)-methanandamide. Tests with SR-141716 (1 and 10 mg/kg) alone resulted in <3% Delta9-THC-appropriate responding. With 10 mg/kg SR-141716, response rate was significantly lower as compared to the rate observed during a vehicle test. Tests with anandamide (10 and 18 mg/kg) resulted in 41% and 85% (R)-methanandamide-appropriate responding at a 3-min pre-treatment time, but in a maximum of 15% (R)-methanandamide-appropriate responding at a longer (15 min) pre-treatment time. In the Delta9-THC (1.8 and 5.6 mg/kg) trained rats, anandamide never produced more than about 20% Delta9-THC-appropriate responding. The results add to a growing body of evidence indicating that there are both similarities and dissimilarities between classical cannabinoids such as THC and endogenous fatty acid ethanolamides.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 21
- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
- Inhibition of the endocannabinoid-regulating enzyme monoacylglycerol lipase elicits a CB1 receptor-mediated discriminative stimulus in mice. Neuropharmacology October 2017
- Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice. Neuropharmacology June 2015
- Endocannabinoid contribution to Δ9-tetrahydrocannabinol discrimination in rodents. European Journal of Pharmacology August 15, 2014
and 16 more in the library
Cites 6
- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999
- Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats. Psychopharmacology December 1998
- Evaluation of cannabimimetic effects of structural analogs of anandamide in rats. European Journal of Pharmacology August 21, 1998
- Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoroanandamide in rhesus monkeys. Pharmacology, Biochemistry, and Behavior December 1997
- (R)-methanandamide, but not anandamide, substitutes for delta 9-THC in a drug-discrimination procedure. Experimental and Clinical Psychopharmacology August 1997
and 1 more in the library