Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys
Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys
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DOI：
10.1038/npp.2008.3
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发表时间：
2009-02-01
影响因子：
7.6
通讯作者：
Nader, Michael A.
中科院分区：
文献类型：
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作者：
Czoty, Paul W.;Riddick, Natallia V.;Nader, Michael A.
据报道，多种涉及多巴胺 (DA) 神经传递功能障碍的情感和神经退行性疾病存在性别差异。此外，有证据表明，在整个月经周期中，对精神兴奋剂滥用相关影响的敏感性存在差异，这可能是由于卵巢激素对 DA 功能的影响所致。本研究的目标是使用选择性 D2 样受体配体 [F-18]氟氯波必利 (FCP) 和高分辨率 microPET P4 扫描仪，将之前检查人类 DA D2 受体可用性与月经周期相关变化的工作扩展到未接受药物的雌性食蟹猴 (n=7)。月经周期阶段的特征是每日阴道拭子和血清黄体酮水平的测量。 PET 研究在黄体期进行一次，在卵泡期进行一次。尾状核、壳核和小脑的感兴趣区域是在配准 MRI 上定义的。计算每个结构中 FCP 的分布体积，并使用两个大脑区域相对于小脑的分布体积比 (DVR) 作为 D2 受体可用性的衡量标准。与卵泡期相比，黄体期尾状核（11.7% 差异，p = 0.02）和壳核（11.6% 差异，p = 0.03）的 FCP DVR 显着更高。这些发现扩展了人类的早期研究，并表明 DA 受体可用性的变化可能与月经周期中各种神经精神疾病症状的变化有关，包括对兴奋剂滥用相关影响的敏感性差异。
Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [F-18]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p = 0.02) and putamen (11.6% difference, p = 0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.