Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia
Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia
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DOI：
10.1111/j.0953-816x.2004.03356.x
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Kelly, PH
中科院分区：
文献类型：
--
作者：
Lecourtier, L;Neijt, HC;Kelly, PH
认知障碍是精神分裂症的一个显著特征。目前对于这种疾病的病因尚无广为接受的解释，但近期的证据表明缰核功能障碍可能与之有关。因此，我们研究了在斯普拉格 - 道利大鼠中缰核损伤是否会导致类似于精神分裂症的行为变化。大鼠接受缰核损伤、假手术或覆盖其上的背侧海马的小损伤（以此检查所观察到的效应不是由于对该结构的意外损伤所致）。由于精神分裂症存在社会行为、感觉运动门控和认知方面的改变，我们对可比的行为进行了检测。在与一只陌生的幼年同种个体5分钟的接触过程中测量社会互动时间。通过不同振幅的前脉冲测量作为感觉运动门控指标的听觉惊跳反应的前脉冲抑制，并在莫里斯水迷宫任务中评估空间认知表现。组织学分析显示，缰核损伤双侧显著损害内侧和外侧缰核，同时在很大程度上不损伤邻近结构。对缰核 - 脚间束的脚间核终末区域的胆碱乙酰转移酶（ChAT）的测定表明，缰核损伤的动物该酶显著减少（减少80%）。与假手术对照组相比，缰核损伤的大鼠（而非背侧海马有小损伤的对照组）在莫里斯迷宫表现上有显著损害。两个损伤组的社会互动时间和前脉冲抑制均无显著改变。这些结果与缰核在认知中的作用一致，也与缰核的病理可能导致精神分裂症的认知障碍这一观点相符。
Cognitive impairment is a prominent feature of schizophrenia. Currently there is no well-accepted explanation of the aetiology of this disorder, but recent evidence indicates that dysfunction of the habenula may be involved. We therefore examined whether habenula lesions in Sprague-Dawley rats cause behavioural changes resembling those of schizophrenia. Rats received either habenula lesions, a sham operation or a small lesion of the overlying dorsal hippocampus as a check that effects observed were not due to incidental damage to this structure. As there are alterations of social behaviour, sensorimotor gating and cognition in schizophrenia, we examined comparable behaviours. Social interaction time was measured during a 5-min encounter with a novel juvenile conspecific. Prepulse inhibition of an acoustic startle response, as an index of sensorimotor gating, was measured with prepulses of various amplitudes, and spatial cognitive performance was assessed in the Morris water maze task. Histological analysis showed that habenula lesions substantially damaged both medial and lateral habenula bilaterally while largely sparing neighbouring structures. Assay of choline acetyltransferase (ChAT) in the interpeduncular nucleus terminal region of the habenulo-interpeduncular tract, showed marked reduction (by 80%) in habenula-lesioned animals. Habenula-lesioned rats, but not the control group with small dorsal hippocampus lesions, showed marked impairment of Morris maze performance compared to the sham-operated control group. Social interaction time and prepulse inhibition were not significantly altered in either lesion group. The results are consistent with a role of the habenula in cognition, and with the view that pathology of the habenula may contribute to the cognitive impairments of schizophrenia.