Journal article
Pharmacokinetic factors in sex differences in Δ9-tetrahydrocannabinol-induced behavioral effects in rats
Behavioural brain research, Vol.154(1), pp.77-83
2004
Handle:
https://hdl.handle.net/2376/110164
Abstract
Cannabinoids have been shown to produce greater behavioral effects in female than in male rats. Sex differences in the metabolism of Δ9-tetrahydrocannabinol (Δ9-THC) have also been demonstrated in one study. The goal of this study was to determine if sex differences in Δ9-THC disposition or metabolism could explain sex differences in Δ9-THC-induced behavioral effects. []-Δ9-THC was administered intraperitoneally (i.p.) to rats and the presence of []-Δ9-THC and metabolites in serum and brain tissue were compared at multiple times post-injection in male versus female rats. Serum levels of Δ9-THC and its metabolites were similar in males and females. In brain tissue, []-Δ9-THC levels also were similar in males and females. In contrast, levels of Δ9-THC metabolites in brain tissue, including 11-hydroxy-Δ9-THC, the major active metabolite, were higher in females than in males. To further investigate if greater production of active metabolites by females explained the greater Δ9-THC-induced behavioral effects observed in females, i.p. Δ9-THC-induced antinociception (50 °C warm water tail withdrawal assay) and catalepsy (bar test) were compared in male and female rats following pretreatment with saline or SKF525A, a cytochrome P450 inhibitor. SKF525A did not affect basal responding in the tail withdrawal assay or bar test in either sex. SKF525A significantly attenuated Δ9-THC-induced antinociception only in females. A similar sex difference was observed in the effects of SKF525A on Δ9-THC-induced catalepsy. These results suggest that the greater levels of active Δ9-THC metabolites produced by females contribute to greater behavioral effects of Δ9-THC in female compared to male rats.
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Details
- Title
- Pharmacokinetic factors in sex differences in Δ9-tetrahydrocannabinol-induced behavioral effects in rats
- Creators
- Alan H TSENG - Program in Pharmacology and Toxicology, Washington State University, Pullman, WA 99164-6534, United StatesJoseph W HARDING - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-6520, United StatesRebecca M CRAFT - Department of Psychology, Washington State University, Pullman, WA 99164-4820, United States
- Publication Details
- Behavioural brain research, Vol.154(1), pp.77-83
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Science; Shannon
- Identifiers
- 99900547151701842
- Language
- English
- Resource Type
- Journal article