Munro Cynthia A, McCaul Mary E, Wong Dean F, Oswald Lynn M, Zhou Yun, Brasic James, Kuwabara Hiroto, Kumar Anil, Alexander Mohab, Ye Weiguo, Wand Gary S
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Biol Psychiatry. 2006 May 15;59(10):966-74. doi: 10.1016/j.biopsych.2006.01.008. Epub 2006 Apr 17.
Sex differences in addictive disorders have been described. Preclinical studies have implicated the striatal dopamine system in these differences, but human studies have yet to substantiate these findings.
Using positron emission tomography (PET) scans with high-specific-activity [11C] raclopride and a reference tissue approach, we compared baseline striatal dopamine binding potential (BP) and dopamine release in men and women following amphetamine and placebo challenges. Subjective drug effects and plasma cortisol and growth hormone responses were also examined.
Although there was no sex difference in baseline BP, men had markedly greater dopamine release than women in the ventral striatum. Secondary analyses indicated that men also had greater dopamine release in three of four additional striatal regions. Paralleling the PET findings, men's ratings of the positive effects of amphetamine were greater than women's. We found no sex difference in neuroendocrine hormone responses.
We report for the first time a sex difference in dopamine release in humans. The robust dopamine release in men could account for increased vulnerability to stimulant use disorders and methamphetamine toxicity. Our findings indicate that future studies should control for sex and may have implications for the interpretation of sex differences in other illnesses involving the striatum.
成瘾性疾病中的性别差异已被描述。临床前研究表明纹状体多巴胺系统与这些差异有关，但人体研究尚未证实这些发现。
使用高比活度[11C]雷氯必利的正电子发射断层扫描（PET）以及参考组织法，我们比较了男性和女性在使用苯丙胺和安慰剂激发后的基线纹状体多巴胺结合潜能（BP）和多巴胺释放情况。还检查了主观药物效应以及血浆皮质醇和生长激素反应。
尽管基线BP无性别差异，但男性腹侧纹状体中的多巴胺释放明显多于女性。二次分析表明，在另外四个纹状体区域中的三个区域，男性的多巴胺释放也更多。与PET结果一致，男性对苯丙胺积极效应的评分高于女性。我们发现神经内分泌激素反应无性别差异。
我们首次报告了人类多巴胺释放存在性别差异。男性强大的多巴胺释放可能解释了对兴奋剂使用障碍和甲基苯丙胺毒性易感性增加的原因。我们的研究结果表明，未来的研究应考虑性别因素，这可能对解释涉及纹状体的其他疾病中的性别差异具有启示意义。
