出生后腹侧下托的功能失活增强氯胺酮注射后成年大鼠延髓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
摘要：
近二十年来，精神分裂症一直被认为是一种功能性分离障碍。大脑几个区域之间的功能性断开可能有神经发育的起源。不同的研究方法表明腹侧下托（Ventral subiculum，VXD）是精神分裂症神经发育障碍的一个特定靶区。精神分裂症患者存在纹状体多巴胺能（DA）调节异常，这可能与海马下丘-纹状体NMDA受体阻断有关。本研究的目的是调查，在成年大鼠，非竞争性NMDA受体拮抗剂氯胺酮对DA反应腹侧纹状体，或更具体地说，核的核心部分，出生后的功能失活的纹状体（Nacc）。在出生后第8天（PND 8），即在神经发育期的关键点，通过局部河豚毒素（TTX）显微注射进行左丘脑的功能失活。在自由活动的成年大鼠（11周）中使用体内伏安法记录DA变化。自发活动的同时记录细胞外DA水平的核心部分的Nacc。本研究期间获得的数据显示，氯胺酮给药后，TTX动物的两个指数高于PBS动物，这表明在PND 8时在左丘脑显微注射TTX的动物对氯胺酮的反应性高于显微注射PBS的动物。这些发现可能提供了新的信息，在精神分裂症的病理生理学的Nacc的核心部分的NMDA受体的参与。
英文摘要：
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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