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.

中文翻译：

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成年大鼠注射氯胺酮后，腹侧下丘脑的产后功能失活增强伏隔核核心部分的多巴胺能反应。

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断开可能是神经发育起源的。各种方法表明，腹侧下丘脑（SUB）是精神分裂症中神经发育障碍的特定目标区域。还普遍公认的是，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受体的细晶下-纹状体分离。本研究旨在研究成年大鼠在产后功能后非竞争性NMDA受体拮抗剂氯胺酮对腹侧纹状体或更确切地说伏隔核（Nacc）核心部分DA反应的影响。 SUB的灭活。在出生后第8天（PND8），即在神经发育时期的关键时刻，通过局部河豚毒素（TTX）显微注射实现了左SUB的功能失活。使用体内伏安法在自由移动的成年大鼠（11周）中记录DA的变化。在Nacc的核心部分与DA的细胞外水平同时记录运动能力。在本研究中获得的数据表明，在施用氯胺酮后，TTX动物中的两个指数高于PBS动物，这表明在PND8左SUB微量注射TTX的动物对氯胺酮的反应性比微量注射PBS的动物更高。