Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients.
Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients.
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DOI：
10.1001/archpsyc.1994.03950020063007
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发表时间：
1994-02
影响因子：
--
通讯作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer
中科院分区：
文献类型：
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作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer
精神病学研究人员需要特定的动物模型来更好地了解精神分裂症的神经生物学。前脉冲抑制（PPI），减少惊吓产生的前脉冲刺激，是减少精神分裂症患者。从理论上讲，精神分裂症患者的PPI不足反映了感觉运动门控的丧失，可能导致感觉洪水和认知碎片。在大鼠中，PPI被多巴胺激动剂的全身给药或通过连接边缘皮质、纹状体、苍白球和脑桥网状结构的神经回路的操纵而破坏。这种大鼠PPI的丢失可能是一个有用的模型，用于研究精神分裂症患者感觉运动门控受损的神经生物学。我们评估了该动物模型的面部、预测和结构效度。支持表面有效性：刺激操作在人类和大鼠中产生了平行的PPI变化，多巴胺激动剂阿扑吗啡破坏了大鼠的PPI，模拟了精神分裂症患者的PPI缺陷。支持预测有效性：抗精神病药物恢复阿扑吗啡治疗大鼠PPI的能力与临床抗精神病药物效力（rs = 0.991）和D2受体亲和力（rs = 0.893）相关。在阿扑吗啡处理的大鼠中恢复PPI的抗精神病药物包括“典型”抗精神病药物和“非典型”抗精神病药物氯氮平。支持结构效度：当多巴胺被注入大鼠的丘脑核时，PPI被破坏;这种作用被氟哌啶醇阻断。多巴胺激活大鼠PPI的丢失可能是精神分裂症患者感觉运动门控缺陷的有效动物模型。这个模型可以帮助我们理解精神分裂症患者认知缺陷的神经生物学。
Psychiatric researchers need specific animal models to better understand the neurobiology of schizophrenia. Prepulse inhibition (PPI), the reduction in startle produced by a prepulse stimulus, is diminished in schizophrenic patients. Theoretically, deficient PPI in schizophrenic patients reflects a loss of sensorimotor gating that may lead to sensory flooding and cognitive fragmentation. In rats, PPI is disrupted by systemic administration of dopamine agonists or by manipulations of neural circuitry linking the limbic cortex, striatum, pallidum, and pontine reticular formation. This loss of PPI in rats may be a useful model for studying the neurobiology of impaired sensorimotor gating in schizophrenic patients. We assessed the face, predictive, and construct validity of this animal model. Face validity was supported: stimulus manipulations produced parallel changes in PPI in humans and rats, and the dopamine agonist apomorphine disrupted PPI in rats, mimicking PPI deficits in schizophrenics. Predictive validity was supported: the ability of antipsychotics to restore PPI in apomorphine-treated rats correlated with clinical antipsychotic potency (rs = .991) and D2-receptor affinity (rs = .893). Antipsychotics that restore PPI in apomorphine-treated rats include "typical" antipsychotics and the "atypical" antipsychotic clozapine. Construct validity was supported: PPI was disrupted in rats when dopamine was infused into the nucleus accumbens; this effect was blocked by haloperidol. The loss of PPI in dopamine-activated rats may be a valid animal model of sensorimotor gating deficits in schizophrenic patients. This model may help us understand the neurobiology of cognitive deficits in schizophrenic patients.