Accepted manuscript
Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat
Drug and alcohol dependence, Vol.143(1), pp.22-28
10/01/2014
Handle:
https://hdl.handle.net/2376/110332
PMCID: PMC4161674
PMID: 25131716
Abstract
•Females show greater THC tolerance than males on two nociceptive assays.•Greater tolerance developed in females given a 30% lower tolerance induction dose.•A moderate dose of chronic THC did not disrupt estrous cycling.
Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats.
Cumulative dose-effect curves were obtained for THC (1.0–18mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined.
On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4mg/kg/injection in females and 7.6mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females.
These results demonstrate that—even when sex differences in acute THC potency are controlled—females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure.
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Details
- Title
- Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat
- Creators
- Alexa A Wakley - Department of Psychology, Washington State University, Pullman, WA 99164-4820, USAJenny L Wiley - RTI International, Research Triangle Park, NC 27709-2194, USARebecca M Craft - Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA
- Publication Details
- Drug and alcohol dependence, Vol.143(1), pp.22-28
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier Ireland Ltd
- Number of pages
- 7
- Grant note
- DA016644 / 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 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
- 99900547118901842
- Language
- English
- Resource Type
- Accepted manuscript