Effects of the PCP analog dizocilpine on sensory gating: Potential relevance to clinical subtypes of schizophrenia
Effects of the PCP analog dizocilpine on sensory gating: Potential relevance to clinical subtypes of schizophrenia
复制标题
DOI：
10.1016/0006-3223(95)00485-8
复制
发表时间：
1996-10-15
影响因子：
10.6
通讯作者：
Schwarzkopf, SB
中科院分区：
文献类型：
--
作者：
AlAmin, HA;Schwarzkopf, SB
听觉惊吓反射的脉冲前抑制（PPI）是一种感觉门控的测量，在精神分裂症患者中降低。多巴胺激动剂和NMDA受体拮抗剂如苯环利定（PCP）可以破坏动物的PPI，这与精神分裂症的多巴胺和谷氨酸假说一致。在这项研究中，我们试图进一步表征NMDA拮抗剂二唑西平对声惊吓调制的影响。Fischer 344大鼠在三种剂量（0.05、0.2和0.5 mg/kg）中的一种剂量后进行测试，并评估PPI以及基线惊吓和脉冲前促进（PPF）的变化。结果显示，在0.2和0.5 mg/kg的二唑西平作用下，每种抑制试验类型的PPI均完全中断。低剂量时基线惊吓和PPF增强，中、高剂量时基线惊吓和PPF降低。虽然二唑西平引起的惊悸前脉调的改变与多巴胺激动剂相似，但有些效果不同。本文讨论了二唑西平对感觉门控的独特作用，以及它们在区分具有不同潜在病理生理的精神分裂症疾病亚型方面的潜力。
Prepulse inhibition (PPI) of the acoustic startle reflex, a measure of sensory gating, is reduced is schizophrenic patients. Dopamine agonists and NMDA receptor antagonists such as phencyclidine (PCP) can disrupt PPI in animals, consistent with both the dopamine and glutamate hypotheses of schizophrenia. In this study, we sought to further characterize the effects of the NMDA antagonist dizocilpine on acoustic startle modulation. Fischer 344 rats were tested after one of three doses of dizocilpine (0.05, 0.2, and 0.5 mg/kg) and assessed for PPI as well as for alterations in baseline startle and prepulse facilitation (PPF). Results showed complete disruption of PPI for each inhibitory trial type after 0.2 and 0.5 mg/kg of dizocilpine. Baseline startle and PPF were enhanced by the low dose but decreased with the moderate and high doses of dizocilpine. Although dizocilpine caused alterations in prepulse modulation of startle similar to dopamine agonists, some effects differ. Unique effects of dizocilpine on sensory gating are discussed in terms of their potential for discriminating subtypes of schizophrenic illness with different underlying pathophysiology.