Muneoka Katsumasa T, Shirayama Yukihiko, Minabe Yoshio, Takigawa Morikuni
Department of Neuropsychiatry, Kagoshima University Faculty of Medicine, Kagoshima, Japan.
Brain Res. 2002 Nov 29;956(2):332-8. doi: 10.1016/s0006-8993(02)03567-9.
Neuronal dysfunction in the frontal cortex has been reported in the etiology of mental disorders, including schizophrenia. The adenosine A(1) receptor system, as well as the dopaminergic system, are important in the control of cortical neuronal activity. We hypothesize that neuroexcitability in early life is critical to the normal development of the brain, and neurosteroids are factors that modulate neuroexcitability during the development period. In this study, we treated neonatal rats with a neurosteroid, pregnenolone (10 microg/g) from postnatal day (PD) 3 until PD 7. In pregnenolone-treated male and female rats, adenosine A(1) receptor density, the amount of dopamine (DA), serotonin (5-HT) and their metabolites in the fronto-parietal cortex and behavioral responses in the open field were examined pre- and post-puberty. A decrease in K(d) values for the adenosine A(1) receptor binding assay using [(3)H]1,3-dipropyl-8-cyclopentylxanthine (DPCPX), increased formation of DA metabolites and hyper-locomotor activity in the open field were found in pregnenolone-treated rats compared with controls in pre- and post-puberty. An increase in 5-HT metabolites was found in the pregnenolone-treated rats in pre-puberty, but not post-puberty. These effects of pregnenolone were not different between males and females. However, correlations between horizontal and vertical activities in the open field were disrupted only in pregnenolone-treated females. The present results indicate that pregnenolone treatment during the neonatal period influences the cortical dopaminergic and adenosinergic systems as well as behavioral responses in the open field.
据报道，包括精神分裂症在内的精神障碍病因中存在额叶皮质的神经元功能障碍。腺苷A(1)受体系统以及多巴胺能系统在控制皮质神经元活动中起着重要作用。我们假设生命早期的神经兴奋性对大脑的正常发育至关重要，而神经甾体是在发育期间调节神经兴奋性的因素。在本研究中，我们从出生后第3天（PD）至PD 7天用神经甾体孕烯醇酮（10微克/克）处理新生大鼠。在孕烯醇酮处理的雄性和雌性大鼠中，在青春期前后检测了额顶叶皮质中腺苷A(1)受体密度、多巴胺（DA）、5-羟色胺（5-HT）及其代谢产物的含量以及旷场中的行为反应。与对照组相比，在青春期前后，孕烯醇酮处理的大鼠在使用[(3)H]1,3-二丙基-8-环戊基黄嘌呤（DPCPX）进行腺苷A(1)受体结合测定时K(d)值降低、DA代谢产物形成增加以及旷场中的运动活性增强。在青春期前，孕烯醇酮处理的大鼠中5-HT代谢产物增加，但在青春期后没有增加。孕烯醇酮的这些作用在雄性和雌性之间没有差异。然而，仅在孕烯醇酮处理的雌性大鼠中，旷场中水平和垂直活动之间的相关性被破坏。目前的结果表明，新生儿期用孕烯醇酮处理会影响皮质多巴胺能和腺苷能系统以及旷场中的行为反应。
