论文标题

成年大鼠注射氯胺酮后,腹侧下调的产后功能失活增强了伏伏核核心部分的多巴胺能反应

Postnatal functional inactivation of the ventral subiculum enhances dopaminergic responses in the core part of the nucleus accumbens following ketamine injection in adult rats

论文作者

Saoud, Hana, De Beus, Duco, Eybrard, Severine, Louilot, Alain

论文摘要

近二十年来,精神分裂症一直被认为是一种功能性断开障碍。几个大脑区域之间的这种功能障碍可能具有神经发育起源。各种方法表明腹侧下调(子)是精神分裂症神经发育障碍的特定靶区域。人们通常也承认,精神分裂症中存在纹状体多巴胺能(DA)失调,这可能取决于涉及谷氨酸能NMDA受体的下纹状体断裂连接。本研究旨在在成年大鼠中研究非竞争力NMDA受体拮抗剂氯胺酮对腹侧纹状体中DA反应的影响,或更具体地说,是Accumbens(NACC)的核心部分(NACC)的核心部分。左子子的功能失活是通过局部四毒素(TTX)在产后第8天(PND8)的局部四毒素(TTX)进行的,即在神经发育期的关键点。在自由移动的成年大鼠中使用体内伏安法记录了DA变异(11周)。在NACC的核心部分中,同时记录了运动活性与DA的细胞外水平记录。在本研究中获得的数据表明,在氯胺酮给药后,TTX动物中的两个指数高于PBS动物,这一点的建议是,在PND8的左下角对TTX进行了对氯胺酮的反应性更大的反应性高于对PBS的动物的反应性。这些发现可以提供有关NMDA谷氨酸能受体参与NaCC的NACC核心部分的新信息。

For almost two decades schizophrenia has been considered to be a functional disconnection disorder. This functional disconnectivity between several brain regions could have a neurodevelopmental origin. Various approaches suggest the ventral subiculum (SUB) is a particular target region for neurodevelopemental disturbances in schizophrenia. It is also commonly acknowledged that there is a striatal dopaminergic (DA) dysregulation in schizophrenia which may depend on a subiculo-striatal disconnection involving glutamatergic NMDA receptors. The present study was designed to investigate, in adult rats, the effects of the non-competitive NMDA receptor antagonist ketamine on DA responses in the ventral striatum, or, more specifically, the core part of the nucleus accumbens (Nacc), following postnatal functional inactivation of the SUB. Functional inactivation of the left SUB was carried out by local tetrodotoxin (TTX) microinjection at postnatal day 8 (PND8), i.e. at a critical point in the neurodevelopmental period. DA variations were recorded using in vivo voltammetry in freely moving adult rats (11 weeks). Locomotor activity was recorded simultaneously with the extracellular levels of DA in the core part of the Nacc. Data obtained during the present study showed that after administration of ketamine, the two indexes were higher in TTX animals than PBS animals, the suggestion being that animals microinjected with TTX in the left SUB at PND8 present greater reactivity to ketamine than animals microinjected with PBS. These findings could provide new information regarding the involvement of NMDA glutamatergic receptors in the core part of the Nacc in the pathophysiology of schizophrenia.

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