Department of Psychiatry, Ruhr University Bochum, Bochum, Germany.
Pharmacopsychiatry. 2010 May;43(3):99-109. doi: 10.1055/s-0029-1242823. Epub 2010 Feb 3.
Growing evidence indicates the role of the thalamus in schizophrenia. The ventral part of the thalamus has been investigated in a few post-mortem studies, suggesting a possible neurodevelopmental etiology of the reduced neuron number.
Here we adapt a neurodevelopmental animal model, the neonatal excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats. At postnatal day (PD) 7 male pups were bilaterally infused into the VT using ibotenic acid (IBA) or artificial cerebrospinal fluid. Repeated measurements of prepulse inhibition (PPI) of the acoustic startle response, reviewed as a measure of sensorimotor gating deficits in neuropsychiatric disorders such as schizophrenia, were performed during puberty and adulthood.
IBA animals showed lower PPI (p<0.001) compared to controls. The extent of VT lesions correlated negatively with PPI levels (p<0.001). PPI deficits in IBA animals were observed at PD 43 and PPI levels increased significantly after puberty without reaching control levels. Acute or subchronic clozapine treatment did not significantly restore low PPI in IBA rats.
The present data suggest that the VT may be involved in the PPI deficits observed in schizophrenia.
越来越多的证据表明丘脑在精神分裂症中的作用。已有少数尸体研究调查了丘脑的腹侧部分，提示神经元数量减少可能具有神经发育病因。
我们采用一种神经发育动物模型，即新生大鼠大脑兴奋性损伤模型，来研究 Sprague-Dawley 大鼠的腹侧丘脑（VT）。在雄性幼鼠出生后第 7 天，通过立体定位将异硫氰酸（IBA）或人工脑脊液双侧注入 VT。在青春期和成年期，通过听觉惊跳反应的前脉冲抑制（PPI）重复测量来评估感觉运动门控缺陷，这是精神分裂症等神经精神障碍的一种测量方法。
IBA 动物的 PPI 较低（p<0.001），与对照组相比。VT 损伤的程度与 PPI 水平呈负相关（p<0.001）。IBA 动物在 PD43 时出现 PPI 缺陷，青春期后 PPI 水平显著增加，但未达到对照水平。急性或亚慢性氯氮平治疗并不能显著恢复 IBA 大鼠的低 PPI。
本研究数据表明，VT 可能参与了精神分裂症中观察到的 PPI 缺陷。
