Saigusa T, Takada K, Baker S C, Kumar R, Stephenson J D
Department of Neuroscience, Institute of Psychiatry, London, England.
Synapse. 1997 Jan;25(1):37-43. doi: 10.1002/(SICI)1098-2396(199701)25:1<37::AID-SYN5>3.0.CO;2-G.
This study compared the effects of dopamine receptor stimulation in the entorhinal cortex on dopamine release in the nucleus accumbens, measured by in vivo microdialysis in conscious Sprague-Dawley rats, with and without oestradiol and progesterone priming. Nonselective dopamine receptor stimulation with apomorphine reduced dopamine release in the nucleus accumbens, an effect which was prevented by injection of cis-flupenthixol into the entorhinal cortex. Selective D1 receptor stimulation with SKF38393 increased dopamine release, whereas selective D2 receptor stimulation with quinpirole did not affect dopamine release. Combined administration of oestradiol and progesterone potentiated the response to apomorphine and prevented the response to SKF38393. The effects of single hormone administration on the response to apomorphine suggested that the modulation was primarily due to oestradiol enhancing effects of progesterone. Experiments with high [K+] suggested these hormonal effects were exerted predominantly in the entorhinal cortex. The present experiments have demonstrated that dopaminergic modulation of transmission in a cortico-striatal loop linking temporal and prefrontal cortex is regulated by oestradiol and progesterone. Dysfunction in this system in humans may give rise to affective and cognitive symptoms which may, if initiated by a postpartum fall in oestrogen and progesterone concentrations, constitute the core pathophysiology of puerperal psychosis.
本研究通过对清醒的斯普拉格-道利大鼠进行体内微透析，比较了在内嗅皮质刺激多巴胺受体对伏隔核中多巴胺释放的影响，实验分为有或无雌二醇和孕酮预处理两组。用阿扑吗啡进行非选择性多巴胺受体刺激可降低伏隔核中的多巴胺释放，而向内侧嗅皮质注射顺式氟哌噻吨可阻止这种效应。用SKF38393进行选择性D1受体刺激可增加多巴胺释放，而用喹吡罗进行选择性D2受体刺激则不影响多巴胺释放。联合给予雌二醇和孕酮可增强对阿扑吗啡的反应，并阻止对SKF38393的反应。单激素给药对阿扑吗啡反应的影响表明，这种调节主要是由于雌二醇增强了孕酮的作用。高[K+]实验表明，这些激素效应主要在内嗅皮质发挥作用。本实验证明，连接颞叶和前额叶皮质的皮质-纹状体环路中多巴胺能传递的调节受雌二醇和孕酮的调控。人类该系统功能障碍可能导致情感和认知症状，如果这些症状由产后雌激素和孕酮浓度下降引发，则可能构成产褥期精神病的核心病理生理学。
