Sex differences in cocaine-induced behavioral responses, pharmacokinetics, and monoamine levels

被引:114
作者
Festa, ED
Russo, SJ
Gazi, FM
Niyomchai, T
Kemen, LM
Lin, SN
Foltz, R
Jenab, S
Quinones-Jenab, V
机构
[1] CUNY, Hunter Coll, Dept Psychol, New York, NY 10021 USA
[2] Univ Utah, Ctr Human Toxicol, Dept Pharmacol & Toxicol, Salt Lake City, UT USA
关键词
cocaine; sex; gender; dopamine; serotonin; metabolism;
D O I
10.1016/j.neuropharm.2003.11.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Female rats display a more robust behavioral response to acute cocaine administration than do male rats. However, a clear understanding of the biological mechanisms underlying these differences remains elusive. The present study investigated whether sexual dimorphisms in cocaine-induced motor behavior might be based on monoaminergic levels and/or cocaine pharmacokinetics. An acute injection of cocaine (5, 15, 20 or 30 mg/kg) or saline was administered to male and female rats, and behavioral activity was monitored for 3 h. Following acute cocaine or saline administration motor behavior varied according to dose and sex; overall, female rats displayed greater rearing counts and stereotypic scores, greater total locomotor counts at 15, 20, and 30 mg/kg of cocaine, and greater ambulatory counts at 20 and 30 mg/kg of cocaine than did male rats. Neurochemical determinations in post-mortem tissue showed that both male and female rats had increases in total dopamine (DA) in the caudate putamen (CPu) 15 min following cocaine administration. Additionally, male rats had a decrease in dihydroxyphenylacetic acid (DOPAC/ DA turnover. Female rats showed significant reductions in total levels of DA, DOPAC, HVA, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and DOPAC/DA turnover in the nucleus accumbens (NAc). Male rats displayed a reduction only in DOPAC/DA turnover and increases in 5-HT in the NAc following cocaine administration. Furthermore, sex differences in cocaine metabolism were observed where females had greater brain/blood levels of norcocaine and ecgonine methyl ester while male rats had higher blood levels of benzoylecgonine. These results suggest that sex differences in the behavioral responses to cocaine administration could be explained in part by intrinsic differences in both monoaminergic levels and metabolic processes. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:672 / 687
页数:16
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