Di Paolo T
School of Pharmacy, Laval University, Québec, Canada.
Rev Neurosci. 1994 Jan-Mar;5(1):27-41. doi: 10.1515/revneuro.1994.5.1.27.
Sex steroid hormones influence the dopaminergic systems of the hypothalamus as well as the extrahypothalamic regions of the brain in controlling movement and behavior in both humans and animals. This review focuses on the effects of sex steroids on dopaminergic activity in extrahypothalamic brain areas. Among sex steroids, estrogens have been most extensively investigated, and many studies report that estrogens affect behaviors mediated by the basal ganglia, such as in humans suffering from extrapyramidal disorders. Epidemiological and clinical evidence also suggests an influence of estrogens on the vulnerability threshold for schizophrenia and sex differences in the clinical expression of this disease. Clinical observations point to a role of androgenic hormones in Gilles de la Tourette's syndrome. In normal humans, sex steroids were also shown to influence motor and cognitive performance. Biochemical and behavioral studies in animals have also shown the effect of sex steroids on dopaminergic activity in the basal ganglia; however, both activating and inhibiting effects have been reported. This may partly be explained by effects of the dose, duration of treatment, interval between steroid administration and testing the behavior measured, and the part of the basal ganglia from which the behavior is elicited. In view of the numerous variables that influence net dopaminergic response to steroids, focus will be on the literature using similar experimental conditions to assess the effect of in vivo chronic steroid treatment, acute short-term steroid treatment and the estrous cycle as well as in vitro effects of steroids on dopamine receptors. These experimental paradigms point to two general mechanisms of action of steroids: a rapid short-term non-genomic membrane effect and a slower long-term possibly genomic effect of steroids on dopamine systems. Combining dopaminergic drugs with sex steroids could improve efficacy or reduce side effects associated with these drugs. Examples of such combined treatments in rats and monkeys are presented for delta 9-tetrahydrocannabinol, cocaine, neuroleptics, apomorphine and L-DOPA. A better understanding of steroid-dopamine interactions and the possible isolation of conditions to have only pro or anti dopaminergic activity could then be used to develop combined therapies or to optimize drug treatments that would take into account the patient's sex and endocrine status.
性类固醇激素会影响下丘脑的多巴胺能系统以及大脑的下丘脑外区域，从而控制人类和动物的运动及行为。本综述聚焦于性类固醇对下丘脑外脑区多巴胺能活性的影响。在性类固醇中，雌激素受到了最为广泛的研究，许多研究报告称，雌激素会影响由基底神经节介导的行为，比如患有锥体外系疾病的人类。流行病学和临床证据也表明，雌激素会影响精神分裂症的易感性阈值以及该疾病临床表现中的性别差异。临床观察指出雄激素类激素在抽动秽语综合征中所起的作用。在正常人类中，性类固醇也被证明会影响运动和认知表现。动物的生化和行为研究也表明了性类固醇对基底神经节中多巴胺能活性的影响；然而，既有激活作用也有抑制作用的报告。这可能部分是由剂量、治疗持续时间、类固醇给药与所测量行为测试之间的间隔以及引发行为的基底神经节部分的影响所解释的。鉴于影响对类固醇的多巴胺能净反应的众多变量，重点将放在使用相似实验条件来评估体内慢性类固醇治疗、急性短期类固醇治疗和发情周期的影响以及类固醇对多巴胺受体的体外影响的文献上。这些实验范式指出了类固醇作用的两种一般机制：类固醇对多巴胺系统的快速短期非基因组膜效应和较慢的长期可能的基因组效应。将多巴胺能药物与性类固醇联合使用可以提高疗效或减少与这些药物相关的副作用。文中给出了大鼠和猴子中此类联合治疗用于Δ⁹ - 四氢大麻酚、可卡因、抗精神病药物、阿扑吗啡和左旋多巴的例子。更好地理解类固醇 - 多巴胺相互作用以及可能分离出仅具有促多巴胺能或抗多巴胺能活性的条件，然后可用于开发联合疗法或优化药物治疗，这将考虑到患者的性别和内分泌状态。
