Startle and sensorimotor gating in rats lacking CCK-A receptors
Startle and sensorimotor gating in rats lacking CCK-A receptors
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DOI：
10.1016/s0893-133x(00)00235-9
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发表时间：
2001-06-01
影响因子：
7.6
通讯作者：
Shilling, PD
中科院分区：
文献类型：
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作者：
Feifel, D;Priebe, K;Shilling, PD
大冢龙埃文斯德岛脂肪（OLETF）大鼠缺乏CCK-A受体，因为基因突变。已有研究表明，CCK-A受体可能在惊吓反射的前脉冲抑制（PPI）和感觉运动门控的操作测量中起作用。本研究研究了OLETF大鼠及其非突变对应物Long Evans德岛大冢（LETO）大鼠的基线和药物破坏PPI。两种基因型大鼠的基线PPI无显著差异，但OLETF大鼠的声惊吓反应高于LETO大鼠。安非他明（2毫克/公斤），和非竞争性NMDA拮抗剂，地佐环平（0.1毫克/公斤），破坏PPI在LETO大鼠，但不是在OLETF大鼠。阿扑吗啡（0.5 mg/kg）未能破坏PPI在LETO和OLETF大鼠，氟哌啶醇（0.5 mg/kg）产生了相当的促进PPI在两组中。在一项单独的研究中，OLETF大鼠被发现对安非他明的运动刺激作用不太敏感。这些结果表明CCK-A受体在苯丙胺和地佐环平的行为效应中起重要作用。OLETF大鼠对苯丙胺和地佐环平的PPI反应与用非典型抗精神病药物预处理的正常大鼠相似，表明CCK-A受体可能在抗精神病药物恢复药物破坏的PPI中起重要作用。(C)2001年美国神经精神药理学学会。出版社：Elsevier Science Inc.
Otsuka Long Evans Tokushima Fatty (OLETF) rats lack CCK-A receptors because of a genetic mutation. Previous studies have shown that CCK-A receptors seem to play a role in the regulation of prepulse inhibition (PPI) of the startle reflex, and operational measure of sensorimotor gating. This study investigated baseline and drug-disrupted PPI in OLETF rats and their non-mutant counterparts, Long Evans Tokushima Otsuka (LETO) rats. Baseline PPI did not differ significantly between the two rat genotypes but OLETF rats exhibited a higher acoustic startle response compared to LETO rats. Amphetamine (2 mg/kg), and the non-competitive NMDA antagonist, dizocilpine (0.1 mg/kg), disrupted PPI in LETO rats but not in the OLETF rats. Apomorphine (0.5 mg/kg) failed to disrupt PPI in both LETO and OLETF rats, and haloperidol (0.5 mg/kg) produced a comparable facilitation of PPI in both groups. In a separate study, OLETF rats were found to be less sensitive to the locomotor stimulating effects of amphetamine. These results suggest that CCK-A receptors play a significant role in the behavioral effects of amphetamine and dizocilpine. The PPI response of OLETF rats to amphetamine and dizocilpine is similar to normal rats pretreated with atypical antipsychotics, suggesting that CCK-A receptors may play an important role in the restoration of drug-disrupted PPI by antipsychotics. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.