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Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats.
Behav Brain Res. 2004 Sep 23; 154(1):77-83.BB

Abstract

Cannabinoids have been shown to produce greater behavioral effects in female than in male rats. Sex differences in the metabolism of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) have also been demonstrated in one study. The goal of this study was to determine if sex differences in Delta(9)-THC disposition or metabolism could explain sex differences in Delta(9)-THC-induced behavioral effects. [(3)H]-Delta(9)-THC was administered intraperitoneally (i.p.) to rats and the presence of [(3)H]-Delta(9)-THC and metabolites in serum and brain tissue were compared at multiple times post-injection in male versus female rats. Serum levels of Delta(9)-THC and its metabolites were similar in males and females. In brain tissue, [(3)H]-Delta(9)-THC levels also were similar in males and females. In contrast, levels of Delta(9)-THC metabolites in brain tissue, including 11-hydroxy-Delta(9)-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 Delta(9)-THC-induced behavioral effects observed in females, i.p. Delta(9)-THC-induced antinociception (50 degrees 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 Delta(9)-THC-induced antinociception only in females. A similar sex difference was observed in the effects of SKF525A on Delta(9)-THC-induced catalepsy. These results suggest that the greater levels of active Delta(9)-THC metabolites produced by females contribute to greater behavioral effects of Delta(9)-THC in female compared to male rats.

Authors+Show Affiliations

Program in Pharmacology and Toxicology, Washington State University, Pullman, WA 99164-6534, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15302113

Citation

Tseng, Alan H., et al. "Pharmacokinetic Factors in Sex Differences in Delta 9-tetrahydrocannabinol-induced Behavioral Effects in Rats." Behavioural Brain Research, vol. 154, no. 1, 2004, pp. 77-83.
Tseng AH, Harding JW, Craft RM. Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats. Behav Brain Res. 2004;154(1):77-83.
Tseng, A. H., Harding, J. W., & Craft, R. M. (2004). Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats. Behavioural Brain Research, 154(1), 77-83.
Tseng AH, Harding JW, Craft RM. Pharmacokinetic Factors in Sex Differences in Delta 9-tetrahydrocannabinol-induced Behavioral Effects in Rats. Behav Brain Res. 2004 Sep 23;154(1):77-83. PubMed PMID: 15302113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats. AU - Tseng,Alan H, AU - Harding,Joseph W, AU - Craft,Rebecca M, PY - 2003/01/17/received PY - 2003/12/01/revised PY - 2004/01/25/accepted PY - 2004/8/11/pubmed PY - 2004/12/16/medline PY - 2004/8/11/entrez SP - 77 EP - 83 JF - Behavioural brain research JO - Behav Brain Res VL - 154 IS - 1 N2 - Cannabinoids have been shown to produce greater behavioral effects in female than in male rats. Sex differences in the metabolism of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) have also been demonstrated in one study. The goal of this study was to determine if sex differences in Delta(9)-THC disposition or metabolism could explain sex differences in Delta(9)-THC-induced behavioral effects. [(3)H]-Delta(9)-THC was administered intraperitoneally (i.p.) to rats and the presence of [(3)H]-Delta(9)-THC and metabolites in serum and brain tissue were compared at multiple times post-injection in male versus female rats. Serum levels of Delta(9)-THC and its metabolites were similar in males and females. In brain tissue, [(3)H]-Delta(9)-THC levels also were similar in males and females. In contrast, levels of Delta(9)-THC metabolites in brain tissue, including 11-hydroxy-Delta(9)-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 Delta(9)-THC-induced behavioral effects observed in females, i.p. Delta(9)-THC-induced antinociception (50 degrees 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 Delta(9)-THC-induced antinociception only in females. A similar sex difference was observed in the effects of SKF525A on Delta(9)-THC-induced catalepsy. These results suggest that the greater levels of active Delta(9)-THC metabolites produced by females contribute to greater behavioral effects of Delta(9)-THC in female compared to male rats. SN - 0166-4328 UR - https://www.unboundmedicine.com/medline/citation/15302113/Pharmacokinetic_factors_in_sex_differences_in_Delta_9_tetrahydrocannabinol_induced_behavioral_effects_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166432804000804 DB - PRIME DP - Unbound Medicine ER -