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Roles of neuropeptide PACAP in regulating psychomotor functions

神经肽 PACAP 在调节精神运动功能中的作用

基本信息

批准号：
13672283
负责人：
HASHIMOTO Hitoshi
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672283/
关键词：
PACAP mutant mice psychomotor behavior prepulse inhibition schizophrenia neuronal plasticity learning and memory behavioral pharmacology 遺伝子欠損マウスアンフェタミン LTP 記憶好奇心探索行動不安セロトニン SSRI

项目摘要

To investigate the physiological roles of endogenous PACAP in higher-order brain/psychological processes, behavioral and electrophysiological analyses were carried out in PACAP gene knockout (PACAP-l-) mice which was recently generated in this laboratory, and the following results were obtained:1. PACAP-l- mice displayed markedly increased locomotor activity and explosive jumping behavior. These aberrant behaviors were ameliorated by the antipsychotic drug haloperidol and selective serotonin reuptake inhibitor (SSRI).2. Increased exploratory-related and reduced anxiety-related behavior in PACAP-l- mice was demonstrated by zone monitoring in the open field, on the elevated plus maze, and by the emergence and novel object tests.3. PACAP-l- mice exhibited normal prepulse inhibition (PPI) of the acoustic startle response at 4 weeks of age; however, they suffer impairment of PPI after 6 weeks of age.4. This reduced PPI was ameliorated by the psychostimulant, but unaffected by haloperidol.5. In PACAP-l- mice, the induction of long-term potentiation (LTP) of hippocampal synaptic strength was reduced. In addition, PACAP heterozygous mutant mice and PACAP (PAC1) receptor exon 2-targeted mice showed a moderate defect in LTP, suggesting a gene-dosage effect for the PACAP gene.6. The behavioral study revealed impaired memory retention of PACAP-l- mice in several behavioral paradigms.In conclusion, the present study proposes a role of PACAP-ergic neurons in regulating psychomotor behaviors and suggests that the phenotype of PACAP-l- mice in part resembles those in human psychiatric disorders. The present study also provides an insight into the role of PACAP in higher brain functions.

为探讨内源性PACAP在脑/心理高阶过程中的生理作用，以本实验室新近培育的PACAP基因敲除小鼠（PACAP-l-）进行行为学和电生理学分析，获得以下结果： 1． PACAP-1-小鼠表现出显着增加的运动活动和爆发性跳跃行为。这些异常行为可通过抗精神病药物氟哌啶醇和选择性血清素再摄取抑制剂 (SSRI) 得到改善。2． PACAP-1-小鼠中探索相关行为的增加和焦虑相关行为的减少通过开放区域、高架十字迷宫中的区域监测以及出现和新物体测试来证明。3． PACAP-1-小鼠在4周龄时表现出正常的声惊吓反应前脉冲抑制（PPI）；然而，6周龄后PPI受损。4．这种降低的 PPI 可以通过精神兴奋剂得到改善，但不受氟哌啶醇的影响。5。在PACAP-1-小鼠中，海马突触强度的长时程增强(LTP)的诱导降低。此外，PACAP 杂合突变小鼠和 PACAP (PAC1) 受体外显子 2 靶向小鼠在 LTP 中表现出中度缺陷，表明 PACAP 基因存在基因剂量效应。6．行为研究揭示了 PACAP-l- 小鼠在几种行为范式中的记忆保留受损。总之，本研究提出了 PACAP 能神经元在调节精神运动行为中的作用，并表明 PACAP-l- 小鼠的表型部分类似于人类精神疾病的表型。本研究还深入了解 PACAP 在高级大脑功能中的作用。