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甘丙肽受体-3 拮抗剂 SNAP 37889 抑制线索诱导的觅酒行为复燃,并增加酒精偏爱大鼠伏隔核壳内 c-Fos 的表达。

The galanin receptor-3 antagonist, SNAP 37889, inhibits cue-induced reinstatement of alcohol-seeking and increases c-Fos expression in the nucleus accumbens shell of alcohol-preferring rats.

机构信息

1 School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia.

2 School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, VIC, Australia.

出版信息

J Psychopharmacol. 2018 Aug;32(8):911-921. doi: 10.1177/0269881118780015. Epub 2018 Jun 21.

Abstract

INTRODUCTION

This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats.

METHODS

Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.p.) or vehicle, before being tested for cue-induced reinstatement. Administration of SNAP 37889 reduced cue-induced reinstatement of ethanol-seeking behaviour. To examine the effect of SNAP 37889 and cue-induced reinstatement on neuronal activation, c-Fos expression was measured in subregions of the medial prefrontal cortex and nucleus accumbens.

RESULTS

SNAP 37889 administration increased c-Fos immunoreactivity in the nucleus accumbens shell, but was without effect in the nucleus accumbens core and the medial prefrontal cortex. Dual-label Fos/tyrosine hydroxylase immunohistochemistry was used to examine the effects of SNAP 37889 on dopamine neurons in the ventral tegmental area; however, no differences between SNAP 37889 and vehicle-treated rats were found.

CONCLUSIONS

These data support previous findings of galanin-3 receptor involvement in cue-induced reinstatement of alcohol-seeking behaviour, and provide novel evidence that the ability of galanin-3 receptor antagonism to attenuate cue-induced reinstatement relates to activation of the nucleus accumbens shell.

摘要

简介

本研究旨在探讨甘丙肽-3 受体拮抗剂 SNAP 37889 对酒精偏好大鼠大脑中线索诱导复饮后 c-Fos 蛋白表达的影响。

方法

18 只酒精偏好大鼠在存在条件性线索的情况下接受 10%v/v 乙醇的自我给药训练,随后进行消退。然后,大鼠接受 SNAP 37889(30mg/kg,腹腔注射)或载体处理,然后进行线索诱导复饮测试。SNAP 37889 给药减少了酒精寻求行为的线索诱导复饮。为了研究 SNAP 37889 和线索诱导复饮对神经元激活的影响,测量了中前额皮质和伏隔核的亚区中 c-Fos 的表达。

结果

SNAP 37889 给药增加了伏隔核壳中的 c-Fos 免疫反应性,但对伏隔核核心和中前额皮质没有影响。双标 Fos/酪氨酸羟化酶免疫组织化学用于研究 SNAP 37889 对腹侧被盖区多巴胺神经元的影响,但未发现 SNAP 37889 和载体处理大鼠之间的差异。

结论

这些数据支持甘丙肽-3 受体参与线索诱导复饮行为的先前发现,并提供了新的证据,表明甘丙肽-3 受体拮抗作用减弱线索诱导复饮的能力与伏隔核壳的激活有关。

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