Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [¹¹C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of “drug effects” and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).

多巴胺相关神经精神疾病的患病率和对多巴胺增强药物（如兴奋剂）的敏感性存在性别差异，这一点已广为人知。在这里，我们评估了人类大脑多巴胺系统中是否存在可能导致这些影响的性别差异。我们分析了两项独立的 [ ¹¹ C] 雷氯必利 PET 脑成像研究的数据，这些研究使用不同的给药途径测量哌醋甲酯诱导的纹状体多巴胺增加（队列 A = 口服 60 毫克；队列 B = 静脉注射 0.5 毫克/千克；总n = 95; 65 名男性，30 名女性），采用设盲的安慰剂对照设计。与男性相比，女性报告了更强的“药物效应”感觉，并且在腹侧纹状体（伏隔核所在的位置）中对口服和静脉注射哌醋甲酯的多巴胺释放显着增加。相比之下，无论是口服还是静脉给药，哌甲酯诱导的背侧纹状体增加都没有显着差异，血浆中哌甲酯的水平也没有差异。与男性相比，雌性纹状体中哌醋甲酯的多巴胺增加更多，但背侧纹状体没有增加，这表明多巴胺奖励系统特有的敏感性增强，这可能是物质使用障碍和注意力缺陷/多动障碍 (ADHD) 易感性性别差异的基础.