首页> 外文OA文献 >Inhibition of 5 alpha-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation
【2h】

Inhibition of 5 alpha-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

机译:伏伏核中5α还原酶的抑制作用抵消了多巴胺能激活引起的感觉运动门控缺陷

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5 alpha-reductase (5 alpha R), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5 alpha R inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (Delta PPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by Delta PPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 mu g/1 mu l) and in the nucleus accumbens (NAc) shell and core (0.5 mu g/0.5 mu l/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5 alpha R in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. (c) 2011 Elsevier Ltd. All rights reserved.
机译:有力的证据突出了神经甾体和雄激素在精神分裂症中的关键作用。我们最近报道,抑制类固醇5α-还原酶(5αR)是神经类固醇合成和雄激素代谢中的限速酶,在人和动物模型中引起抗精神病样作用,而不会引起锥体束外副作用。为了阐明介导这些作用的解剖学基质,我们研究了周围和神经结构对5 alpha R抑制剂非那雄胺(FIN)对大鼠惊吓反射(ASR)的前脉冲抑制(PPI)的行为影响的作用。可靠地模拟在精神分裂症和其他神经精神疾病中观察到的感觉运动门控障碍的范例。通过以百分比(%PPI)和绝对值(Delta PPI)来衡量该指数,排除了药物引起的ASR修饰对PPI的潜在影响。在经去睾丸和假手术的大鼠中,FIN均能防止多巴胺(DA)受体激动剂阿扑吗啡(APO,0.25 mg / kg,SC)和d-苯异丙胺(AMPH,2.5 mg / kg,SC)引起的%PPI缺乏,尽管Delta PPI分析并未证实后者的影响。相反,APO诱导的PPI不足可通过FIN输注脑室(10μg/ 1μl)和伏隔核(NAc)壳和核(0.5μg/ 0.5μl/侧)来抵消。 FIN注射后在其他脑区域(包括尾状背,基底外侧杏仁核,腹侧海马和前额内侧皮层)未观察到明显的PPI改善作用。全身性给药可增加DA在NAc中的流出,但不增加脑FIN给药。综上所述,这些发现表明5αR在门控调控中的作用是基于NAc中的突触后机制,与该区域DA外排的改变没有直接关系。 (c)2011 Elsevier Ltd.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号