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Dissimilar cannabinoid substitution patterns in mice trained to discriminate Δ(9)-tetrahydrocannabinol or methanandamide from vehicle.
Behav Pharmacol. 2011 Sep; 22(5-6):480-8.BP

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.

Authors+Show Affiliations

RTI International, Research Triangle Park, North Carolina 27709-2194, USA. jwiley@rti.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21712709

Citation

Wiley, Jenny L., et al. "Dissimilar Cannabinoid Substitution Patterns in Mice Trained to Discriminate Δ(9)-tetrahydrocannabinol or Methanandamide From Vehicle." Behavioural Pharmacology, vol. 22, no. 5-6, 2011, pp. 480-8.
Wiley JL, Matthew Walentiny D, Vann RE, et al. Dissimilar cannabinoid substitution patterns in mice trained to discriminate Δ(9)-tetrahydrocannabinol or methanandamide from vehicle. Behav Pharmacol. 2011;22(5-6):480-8.
Wiley, J. L., Matthew Walentiny, D., Vann, R. E., & Baskfield, C. Y. (2011). Dissimilar cannabinoid substitution patterns in mice trained to discriminate Δ(9)-tetrahydrocannabinol or methanandamide from vehicle. Behavioural Pharmacology, 22(5-6), 480-8. https://doi.org/10.1097/FBP.0b013e328348eced
Wiley JL, et al. Dissimilar Cannabinoid Substitution Patterns in Mice Trained to Discriminate Δ(9)-tetrahydrocannabinol or Methanandamide From Vehicle. Behav Pharmacol. 2011;22(5-6):480-8. PubMed PMID: 21712709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissimilar cannabinoid substitution patterns in mice trained to discriminate Δ(9)-tetrahydrocannabinol or methanandamide from vehicle. AU - Wiley,Jenny L, AU - Matthew Walentiny,D, AU - Vann,Robert E, AU - Baskfield,Cassandra Y, PY - 2011/6/30/entrez PY - 2011/6/30/pubmed PY - 2011/12/14/medline SP - 480 EP - 8 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 22 IS - 5-6 N2 - 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. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/21712709/Dissimilar_cannabinoid_substitution_patterns_in_mice_trained_to_discriminate_Δ_9__tetrahydrocannabinol_or_methanandamide_from_vehicle_ L2 - http://dx.doi.org/10.1097/FBP.0b013e328348eced DB - PRIME DP - Unbound Medicine ER -