Habituation and sensitization of acoustic startle: Opposite influences of dopamine D1 and D2-family receptors
Habituation and sensitization of acoustic startle: Opposite influences of dopamine D1 and D2-family receptors
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DOI：
10.1016/j.nlm.2008.05.015
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发表时间：
2009-09-01
影响因子：
2.7
通讯作者：
Geyer, Mark A.
中科院分区：
文献类型：
--
作者：
Halberstadt, Adam L.;Geyer, Mark A.
由重复呈现响亮的声刺激引起的惊吓反应受敏化和习惯化的独立过程调节。虽然精神分裂症与信息处理障碍有关，但关于精神分裂症患者存在习惯化缺陷的证据相互矛盾。然而，最近的临床证据表明，精神分裂症患者表现出过度的惊吓敏感性和减少的习惯性。鉴于多巴胺能异常和精神分裂症之间的联系，本研究的目的是检查删除D-1和D-2样多巴胺受体对小鼠声惊吓反射的敏化和习惯化的影响。对于这些实验，使用可以测量致敏和习惯化的方法，在C57 BL/6 J背景下的多巴胺D-1、D-2和D-3受体野生型（WT）和敲除（KO）小鼠中评估声惊吓反射。缺乏D-1受体基因的小鼠表现出更强的敏感性，沿着出现的习惯性减少，这种习惯性是对重复出现的惊人刺激的反应。相反，多巴胺D-2或D-3受体基因的缺失产生了致敏缺陷和习惯化的显著增加。D-1受体KO小鼠表现出的行为表型明显不同于D-2和D-3受体KO小鼠。在D-1受体KO小鼠中的发现使人想起在类似惊吓范例中测试的精神分裂症患者中观察到的异常，并且表明D-1激动剂可能对与精神分裂症相关的信息处理缺陷具有治疗功效。(C)2008年爱思唯尔公司All rights reserved.
The startle response evoked by repeated presentation of a loud acoustic stimulus is regulated by the independent processes of sensitization and habituation. While schizophrenia is associated with information processing impairments, there is conflicting evidence regarding the existence of habituation deficits in schizophrenic patients. Recent clinical evidence, however, indicates that patients with schizophrenia display exaggerated startle sensitization and diminished habituation. Given the linkage between dopaminergic abnormalities and schizophrenia, the goal of the present investigation was to examine the effect of deleting D-1 and D-2-like dopamine receptors on sensitization and habituation of the acoustic startle reflex in mice. For these experiments, the acoustic startle reflex was assessed in dopamine D-1, D-2, and D-3 receptor wild-type (WT) and knockout (KO) mice on a C57BL/6J background, using a methodology that can measure both sensitization and habituation. Mice lacking the D-1 receptor gene displayed enhanced sensitization, along with a decrease in the amount of habituation that occurs in response to repetitive presentations of a startling stimulus. Conversely, the loss of the dopamine D-2 or D-3 receptor gene produced a sensitization deficit and a significant increase in habituation. The behavioral phenotype exhibited by D-1 receptor KO mice is clearly distinct from that of the D-2 and D-3 receptor KO mice. The findings in D-1 receptor KO mice are reminiscent of the abnormalities observed in schizophrenic patients tested in comparable startle paradigms, and indicate that D-1 agonists may possess therapeutic efficacy against the information processing deficits associated with schizophrenia. (C) 2008 Elsevier Inc. All rights reserved.