Effects of sex and gonadectomy on cocaine metabolism in the rat

The purpose of the current study is to determine whether sex differences in metabolism of cocaine (COC) exist that could contribute to the greater beh avioral sensitivity of females to COC administration. To investigate this q uestion, concentrations of COC and its two principle metabolites benzoylecg onine (BE) and ecgonine methyl ester (EME) were measured by gas chromatogra phy/mass spectroscopy in brain and plasma collected from male and female va ts 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 det ected. BE was 2-fold higher in plasma and brain of males than females, wher eas EME was much higher in brain and plasma of females. The influence of go nadal hormones on COC metabolite patterns were determined using gonadecto-m ized and prepubertal rats. Castration of male or female rats did not alter brain or plasma COG, but did decrease BE concentrations. Seven-day-old pups injected with 15 mg/kg of COC had higher blood and brain COC than adults a nd relatively low levels of metabolites. No sex differences were found for COG, BE, or EME in brain or plasma of pups. These findings indicate that al though gonadal steroids influence COC metabolism, these effects do not expl ain sex differences in COC-induced behaviors.