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新生大鼠胃泌素释放肽受体阻断后社会行为和记忆的损害:对神经发育障碍动物模型的启示。

Impairments of social behavior and memory after neonatal gastrin-releasing peptide receptor blockade in rats: Implications for an animal model of neurodevelopmental disorders.

作者信息

Presti-Torres J, de Lima M N, Scalco F S, Caldana F, Garcia V A, Guimarães M R, Schwartsmann G, Roesler Rafael, Schröder Nadja

机构信息

Neurobiology and Developmental Biology Laboratory and Graduate Program in Cellular and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.

出版信息

Neuropharmacology. 2007 Mar;52(3):724-32. doi: 10.1016/j.neuropharm.2006.09.020. Epub 2006 Nov 13.

Abstract

The gastrin-releasing peptide receptor (GRPR) has been implicated in central nervous system (CNS) diseases, including neurodevelopmental disorders associated with autism. In the present study we examined the effects of GRPR blockade during the neonatal period on behavioral measures relevant to animal models of neurodevelopmental disorders. Male Wistar rats were given an intraperitoneal (i.p.) injection of either saline (SAL) or the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095; 1 or 10mg/kg) twice daily for 10days from postnatal days (PN) 1 to 10. Animals treated with RC-3095 showed pronounced deficits in social interaction when tested at PN 30-35 and impaired 24-h retention of memory for both novel object recognition (NOR) and inhibitory avoidance (IA) tasks tested at PN 60-71. Neither short-term memory tested 1.5h posttraining nor open field behavior were affected by neonatal GRPR blockade. The implications of the findings for animal models of neurodevelopmental disorders are discussed.

摘要

胃泌素释放肽受体(GRPR)与中枢神经系统(CNS)疾病有关,包括与自闭症相关的神经发育障碍。在本研究中,我们研究了新生期GRPR阻断对与神经发育障碍动物模型相关行为指标的影响。雄性Wistar大鼠从出生后第1天(PN)至第10天每天腹腔注射(i.p.)生理盐水(SAL)或GRPR拮抗剂[D-Tpi(6),Leu(13) psi(CH(2)NH)-Leu(14)]蛙皮素(6-14)(RC-3095;1或10mg/kg),每天两次,共10天。在PN 30-35进行测试时,用RC-3095处理的动物在社交互动方面表现出明显缺陷,并且在PN 60-71对新物体识别(NOR)和抑制性回避(IA)任务进行测试时,24小时记忆受损。新生期GRPR阻断对训练后1.5小时测试的短期记忆和旷场行为均无影响。本文讨论了这些发现对神经发育障碍动物模型的意义。

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