ISOLATION REARING OF RATS PRODUCES A DEFICIT IN PREPULSE INHIBITION OF ACOUSTIC STARTLE SIMILAR TO THAT IN SCHIZOPHRENIA
ISOLATION REARING OF RATS PRODUCES A DEFICIT IN PREPULSE INHIBITION OF ACOUSTIC STARTLE SIMILAR TO THAT IN SCHIZOPHRENIA
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DOI：
10.1016/0006-3223(93)90180-l
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发表时间：
1993-09-15
影响因子：
10.6
通讯作者：
ROBBINS, TW
中科院分区：
文献类型：
--
作者：
GEYER, MA;WILKINSON, LS;ROBBINS, TW
精神分裂症患者在惊吓的脉冲前抑制方面表现出缺陷，惊吓是一种对感觉运动门控缺陷的操作测量，理论上认为这是导致认知障碍的原因之一。在大鼠中，中脑边缘多巴胺(DA)的激活破坏了脉冲前抑制，为精神分裂症患者提供了一个类似的感觉运动门控缺陷的有用模型。隔离饲养的大鼠表现出神经化学和行为异常，提示中脑边缘DA系统活动过度。在目前的研究中，对群养或隔离饲养的大鼠进行惊吓反应范式测试，使用120或105分贝的声脉冲，其中一些脉冲之前(100毫秒)的预脉冲比65分贝的背景高2、4、8或16分贝。隔离饲养的动物只对最初的少许惊吓刺激反应过度。在隔离饲养的动物中，预脉冲抑制量显著减少，特别是当使用中档8分贝预脉冲时。随后的一项研究复制了隔离饲养对脉冲前抑制的影响，并提出隔离饲养动物表现出的感觉运动门控缺陷可以通过给予DA拮抗剂雷氯普利(0.05 mg/kg)来正常化。因此，隔离饲养提供了一种非药理学的方法来诱导大鼠感觉运动门控缺陷，这在精神分裂症患者中表现出来。
Schizophrenic patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating deficits that are theorized to contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts prepulse inhibition, providing a useful model of the similar deficits in sensorimotor gating in schizophrenic patients. Rats reared in isolation exhibit neurochemical and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were tested in startle response paradigms using 120 or 105 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65 dB background. Isolation-reared animals were hyperreactive only in response to the initlal few startle stimuli. The amount of prepulse inhibition was decreased significantly in isolation-reared animals, particularly when midrange 8 dB prepulses were used. A subsequent study replicated the effect of isolation rearing on prepulse inhibition and suggested that the deficit in sensorimotor gating exhibited by isolation-reared animals may be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to induce in rats a deficit in sensorimotor gating that is exhibited by schizophrenic patients.