(R)-Methanandamide and Δ9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide

doi:10.1007/s002130100730

Paper

(R)-Methanandamide and Δ9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide

Published Aug 1, 2001 · Järbe T., Lamb R., Lin S.

Psychopharmacology

Q1 SJR score

89

Citations

10

Influential Citations

Full textSemantic Scholar

Abstract

Abstract. Rationale and objectives: (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. Methods: 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 Δ9-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 Δ9-THC. A two lever operant methodology (FR10) was used. Results: Δ9-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 Δ9-THC dose-response curve for Δ9-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 Δ9-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 Δ9-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% Δ9-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 Δ9-THC (1.8 and 5.6 mg/kg) trained rats, anandamide never produced more than about 20% Δ9-THC-appropriate responding. Conclusion: 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.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

(R)-methanandamide and 9-THC are both potent discriminative stimuli in rats, with SR-141716 acting as a cannabinoid antagonist, affecting their ability to cause appropriate responses.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

(R)-Methanandamide and Δ9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide

Sign up to use Study Snapshot

References

Effects of Δ9-tetrahydrocannabinol, (R)-methanandamide, SR 141716, and d-amphetamine before and during daily Δ9-tetrahydrocannabinol dosing

Daily dosing of 9-THC in rats leads to tolerance and cross-tolerance to (R)-methanandamide, with d-amphetamine showing similar effects.

Δ9‐THC training dose as a determinant for (R)‐methanandamide generalization in rats: a systematic replication

Cannabinoid agonists can have varying degrees of efficacy at a receptor site, with the prevailing training-dose condition being the major determinant for substitution patterns in rats.

Cannabis Discrimination of “Internal Bliss”?

Cannabis intoxication and dependence are pharmacologically selective for centrally active cannabinoid compounds, with anandamide playing a less clear role in the process.

SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity.

SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversing tonic CB1 cannabinoid receptor activity.

Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action

Endocannabinoids, found in the brain, activate cannabinoid receptors and play a neuromodulatory role in modulating neurotransmitter action and release.

Citations

Cannabinoid CB1 Discrimination: Effects of Endocannabinoids and Catabolic Enzyme Inhibitors

Combining, but not selective, enhancement of endocannabinoid activity via enzyme inhibition may produce CB1 receptor-mediated subjective effects for therapeutic purposes.

Inhibition of the endocannabinoid-regulating enzyme monoacylglycerol lipase elicits a CB1 receptor-mediated discriminative stimulus in mice

Inhibiting the enzyme MAGL in mice allows for a CB1 receptor-mediated discriminative stimulus, suggesting that it may release an endogenous brake producing effects akin to those produced by exogenously administered cannabinoids.

Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and Synthetic Cannabinoids in the Mouse In Vivo Triad Model

CB1 receptors largely mediate the central pharmacological effects of synthetic cannabinoids, with rimonabant acting as a CB1R antagonist to assess potential receptor heterogeneity.

Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids.

Cannabinoid discrimination studies are valuable for identifying synthetic cannabinoids with potential abuse liability, aiding in regulatory decisions.

[INCREMENT]9-Tetrahydrocannabinol discriminative stimulus effects of AM2201 and related aminoalkylindole analogs in rats

AM2201 and related compounds in 'Spice' exhibit potent cannabinoid-like effects, with AM2201 being 14-fold more potent than THC, and their discrimination is CB1R dependent.