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孤啡肽/孤啡肽FQ受体对幼龄和青春期大鼠乙醇介导的动机效应的药理学特性研究

Pharmacological characterization of the nociceptin/orphanin FQ receptor on ethanol-mediated motivational effects in infant and adolescent rats.

作者信息

Miranda-Morales Roberto Sebastián, Pautassi Ricardo M

机构信息

Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), 5016 Córdoba, Argentina.

Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), 5016 Córdoba, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.

出版信息

Behav Brain Res. 2016 Feb 1;298(Pt A):88-96. doi: 10.1016/j.bbr.2015.04.016. Epub 2015 Apr 20.

Abstract

Activation of nociceptin/orphanin FQ (NOP) receptors attenuates ethanol drinking and prevents relapse in adult rodents. In younger rodents (i.e., infant rats), activation of NOP receptors blocks ethanol-induced locomotor activation but does not attenuate ethanol intake. The aim of the present study was to extend the analysis of NOP modulation of ethanol's effects during early ontogeny. Aversive and anxiolytic effects of ethanol were measured in infant and adolescent rats via conditioned taste aversion and the light-dark box test; whereas ethanol-induced locomotor activity and ethanol intake was measured in adolescents only. Before these tests, infant rats were treated with the natural ligand of NOP receptors, nociceptin (0.0, 0.5 or 1.0 μg) and adolescent rats were treated with the specific agonist Ro 64-6198 (0.0, 0.1 or 0.3 mg/kg). The activation of NOP receptors attenuated ethanol-induced anxiolysis in adolescents only, and had no effect on ethanol's aversive effects. Administration of Ro 64-6198 blocked ethanol-induced locomotor activation but did not modify ethanol intake patterns. The attenuation of ethanol stimulating and anxiolytic effect by activation of NOP receptors indicates a modulatory role of this receptor on ethanol effects, which is expressed early in ontogeny.

摘要

伤害感受素/孤啡肽FQ(NOP)受体的激活可减少成年啮齿动物的乙醇摄入量,并防止复发。在较年幼的啮齿动物(即幼鼠)中,NOP受体的激活可阻断乙醇诱导的运动激活,但不会减少乙醇摄入量。本研究的目的是扩展对早期个体发育过程中NOP对乙醇作用调节的分析。通过条件性味觉厌恶和明暗箱试验,在幼鼠和青春期大鼠中测量乙醇的厌恶和抗焦虑作用;而仅在青春期大鼠中测量乙醇诱导的运动活性和乙醇摄入量。在这些试验之前,给幼鼠注射NOP受体的天然配体伤害感受素(0.0、0.5或1.0μg),给青春期大鼠注射特异性激动剂Ro 64-6198(0.0、0.1或0.3mg/kg)。NOP受体的激活仅减弱了青春期大鼠中乙醇诱导的抗焦虑作用,对乙醇的厌恶作用没有影响。Ro 64-6198的给药阻断了乙醇诱导的运动激活,但没有改变乙醇摄入模式。NOP受体激活对乙醇刺激和抗焦虑作用的减弱表明该受体对乙醇作用具有调节作用,这在个体发育早期就已表现出来。

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