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不同的抗精神病药物通过 Fos 免疫组织化学显示出对大细胞催产素能和加压素能神经元的不同影响。

Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry.

机构信息

Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.

出版信息

J Neurosci Res. 2010 Feb 15;88(3):677-85. doi: 10.1002/jnr.22226.

Abstract

Acute administration of antipsychotics elicits regionally distinct patterns of Fos expression in the rat brain. Stimulation of oxytocin (OXY) and vasopressin (AVP) release in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei indicates that antipsychotics may play a role in autonomic, neuroendocrine, and behavioral processes. This study was focused to reveal the responsiveness of hypothalamic OXY- and AVP- producing magnocellular neurons, in terms of quantitative and topographical distinctions, to antipsychotics displaying different pharmacological profiles. Naive male Wistar rats were injected intraperitoneally with haloperidol (1 mg/kg), clozapine (30 mg/kg), olanzapine (30 mg/kg), risperidone (2mg/kg), and vehicle (5% chremophor) and were sacrificed 60 min later by a fixative. Fos, Fos/OXY, and Fos/AVP labelings were visualized by immunohistochemistry in the SON, 5 accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed in naive or vehicle treated control rats. The data indicate the existence of a substantial diversity in the stimulatory effect of the selected antipsychotics on quantity of Fos, Fos/OXY, and Fos/AVP immunostainings with the preferential action of the atypicals clozapine over olanzapine and little effects of risperidone and haloperidol. Variabilities in Fos distribution in the PVN, SON, and ACS induced by antipsychotics may be helpful to understand more precisely the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences.

摘要

急性给予抗精神病药物会在大鼠大脑中引起区域特异性的 Fos 表达模式。刺激下丘脑室旁核 (PVN) 和视上核 (SON) 中的催产素 (OXY) 和血管加压素 (AVP) 释放表明,抗精神病药物可能在自主神经、神经内分泌和行为过程中发挥作用。这项研究的重点是揭示具有不同药理学特征的抗精神病药物对下丘脑 OXY 和 AVP 产生的大细胞神经元的反应性,包括数量和拓扑上的区别。将雄性 Wistar 大鼠注射腹腔内给予氟哌啶醇 (1mg/kg)、氯氮平 (30mg/kg)、奥氮平 (30mg/kg)、利培酮 (2mg/kg) 和载体 (5% 吐温 80),60 分钟后用固定剂处死。使用计算机化显微镜,通过免疫组织化学在 SON、5 个辅助 (ACS) 细胞群和 4 个不同的 PVN 细分区域中观察到 Fos、Fos/OXY 和 Fos/AVP 标记。氯氮平和奥氮平最明显地激活了单个 Fos、Fos/OXY 和 Fos/AVP 细胞;利培酮和氟哌啶醇的作用明显较低;在未处理或载体处理的对照大鼠中未发现共定位。这些数据表明,在所选择的抗精神病药物对 Fos、Fos/OXY 和 Fos/AVP 免疫染色的数量的刺激作用存在显著差异,其中非典型药物氯氮平的作用优先于奥氮平,而利培酮和氟哌啶醇的作用较小。抗精神病药物诱导的 PVN、SON 和 ACS 中 Fos 分布的变异性有助于更精确地理解它们的大脑外作用的程度,可能推测它们的功能影响和副作用后果。

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