Accepted manuscript
Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats
Drug and alcohol dependence, Vol.172, pp.51-59
03/01/2017
Handle:
https://hdl.handle.net/2376/109255
PMCID: PMC5309167
PMID: 28130989
Abstract
•Female rats are more sensitive to the discriminative stimulus effects of Δ9- tetrahydrocannabinol (THC).•Synthetic cannabinoids (SCBs) produce THC-like effects in rats of both sexes.•Sex differences in rate suppressing effects do not occur for all SCBs.•Disparity across assays precludes pharmacokinetic explanation of results.
Women report greater sensitivity to the subjective effects of Δ9-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats.
A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure.
Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes.
This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC’s effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology.
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Details
- Title
- Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats
- Creators
- Jenny L Wiley - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United StatesTimothy W Lefever - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United StatesJulie A Marusich - RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United StatesRebecca M Craft - Department of Psychology, Washington State University, Pullman, WA 99164-4820, United States
- Publication Details
- Drug and alcohol dependence, Vol.172, pp.51-59
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier B.V
- Number of pages
- 9
- Grant note
- DA-016644; DA-003672 / National Institutes of Health, National Institute on Drug Abuse (NIH/NIDA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) R01DA016644 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Identifiers
- 99900547387601842
- Language
- English
- Resource Type
- Accepted manuscript