Dissimilar cannabinoid substitution patterns in mice trained to discriminate Δ(9)-tetrahydrocannabinol or methanandamide from vehicle.
Jenny L Wiley, D Matthew Walentiny, Robert E Vann, Cassandra Y Baskfield
Behavioural Pharmacology September 2011 DOI: 10.1097/fbp.0b013e328348eced (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Behavioral pharmacology study using drug discrimination procedures in mice Peer reviewed |
|---|---|
| Population | Male and female mice |
| Interventions | THC methanandamide CP 55940 anandamide rimonabant |
| Dose | 30 mg/kg THC, 70 mg/kg methanandamide |
| Topics | Cannabis |
| Key points | THC and CP 55940 fully substituted in THC-trained mice of both sexes and THC substitution was rimonabant-reversible, whereas methanandamide and anandamide did not substantially substitute on the THC lever. In methanandamide-trained mice, methanandamide fully generalized but rimonabant did not reverse it. The authors suggest incomplete overlap between endocannabinoid pharmacology and marijuana intoxication, and a possible non-CB(1) receptor mechanism at higher methanandamide doses. |
Abstract
Δ(9)-Tetrahydrocannabinol (THC) discrimination in rodents is a behavioral assay that has been used to probe differences among classes of cannabinoids in rats. The purpose of this study was to determine whether traditional and anandamide-like cannabinoids were distinguishable in cannabinoid discrimination procedures in mice. Male mice were trained to discriminate 30 mg/kg THC or 70 mg/kg methanandamide from vehicle in a two-lever milk-reinforced drug discrimination procedure. After acquisition, agonist tests with THC, methanandamide, CP 55940, and anandamide were conducted, as were antagonism tests with rimonabant. Substitution (agonism) and antagonism tests were also carried out in female mice trained to discriminate THC. THC and CP 55940 fully substituted in THC-trained mice of both sexes. Further, THC substitution was rimonabant reversible. In contrast, mice injected with methanandamide or anandamide failed to respond substantially on the THC lever, even up to doses that decreased overall responding. In methanandamide-trained mice, methanandamide fully generalized to the methanandamide training dose. Rimonabant did not reverse this generalization. Although THC, CP 55940, and anandamide also increased responding on the methanandamide lever, the magnitude of substitution was less than for methanandamide. These results suggest incomplete overlap in the underlying mechanisms mediating endocannabinoid pharmacology and marijuana intoxication. Further, they suggest that methanandamide discrimination may involve a non-CB(1) receptor mechanism that is particularly prominent at higher doses.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 7
- Sex Differences in the Safety and Subjective Effects of Two Oral Δ9-Tetrahydrocannabinol-Containing Cannabis Products over Multiple Doses Among Healthy Adults. Cannabis and Cannabinoid Research August 2024
- 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 2 more in the library