Effects of sex and gonadectomy on cocaine metabolism in the rat.

Published

Journal Article

The purpose of the current study is to determine whether sex differences in metabolism of cocaine (COC) exist that could contribute to the greater behavioral sensitivity of females to COC administration. To investigate this question, concentrations of COC and its two principle metabolites benzoylecgonine (BE) and ecgonine methyl ester (EME) were measured by gas chromatography/mass spectroscopy in brain and plasma collected from male and female rats that were sacrificed between 5 and 90 min after injection COC (15 mg/kg i.p.). COC concentrations did not differ in plasma or brain tissue of males and females, but sex-specific patterns of metabolite distribution were detected. BE was 2-fold higher in plasma and brain of males than females, whereas EME was much higher in brain and plasma of females. The influence of gonadal hormones on COC metabolite patterns were determined using gonadectomized and prepubertal rats. Castration of male or female rats did not alter brain or plasma COC, but did decrease BE concentrations. Seven-day-old pups injected with 15 mg/kg of COC had higher blood and brain COC than adults and relatively low levels of metabolites. No sex differences were found for COC, BE, or EME in brain or plasma of pups. These findings indicate that although gonadal steroids influence COC metabolism, these effects do not explain sex differences in COC-induced behaviors.

Full Text

Duke Authors

Cited Authors

  • Bowman, BP; Vaughan, SR; Walker, QD; Davis, SL; Little, PJ; Scheffler, NM; Thomas, BF; Kuhn, CM

Published Date

  • September 1999

Published In

Volume / Issue

  • 290 / 3

Start / End Page

  • 1316 - 1323

PubMed ID

  • 10454509

Pubmed Central ID

  • 10454509

International Standard Serial Number (ISSN)

  • 0022-3565

Language

  • eng

Conference Location

  • United States