Suchankova Petra, Engel Jörgen A, Jerlhag Elisabet
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Alcohol Alcohol. 2016 Mar;51(2):121-7. doi: 10.1093/alcalc/agv100. Epub 2015 Aug 31.
Ghrelin initially emerged as a gut-brain hormone controlling food intake, meal initiation and appetite mainly via hypothalamic circuits in both rodents and humans. The findings that ghrelin receptors (GHS-R1A) are expressed in reward-related areas, including the nucleus accumbens (NAc) and ventral tegmental area (VTA), suggest that ghrelin is a novel reward regulator. Indeed, ghrelin signalling mediates the rewarding and motivational properties of addictive drugs. In addition, daily co-administration of a GHS-R1A antagonist and various addictive drugs prevents the drug-induced locomotor sensitization in rats.
The present series of experiment were designed to evaluate the effect of repeated pharmacological GHS-R1A suppression on drug-induced locomotor stimulation in more detail.
We showed that sub-chronic pre-treatment of the GHS-R1A antagonist, JMV2959, attenuated the ability of acute administration of alcohol as well as of amphetamine to stimulate locomotion. However, there was no effect of sub-chronic JMV2959 treatment on locomotor activity per se or on the expression of the GHS-R1A gene (Ghsr) in the VTA or the NAc compared with vehicle treatment. In addition, sub-chronic ghrelin treatment caused a locomotor sensitization.
While previous research has pinpointed ghrelin as an appetite regulator the present study together with previous studies suggest that ghrelin signalling modulates various reward-mediated behaviours in rodents. Collectively, this suggests that the GHS-R1A could be a key target for novel treatment strategies for addiction.
胃饥饿素最初作为一种肠脑激素出现，主要通过啮齿动物和人类的下丘脑回路控制食物摄入、进食起始和食欲。胃饥饿素受体（GHS-R1A）在包括伏隔核（NAc）和腹侧被盖区（VTA）在内的奖赏相关区域表达，这一发现表明胃饥饿素是一种新型奖赏调节因子。事实上，胃饥饿素信号传导介导成瘾药物的奖赏和动机特性。此外，每日联合给予GHS-R1A拮抗剂和各种成瘾药物可预防大鼠药物诱导的运动敏化。
本系列实验旨在更详细地评估反复药理学抑制GHS-R1A对药物诱导的运动刺激的影响。
我们发现，GHS-R1A拮抗剂JMV2959的亚慢性预处理减弱了急性给予酒精和苯丙胺刺激运动的能力。然而，与溶剂处理相比，亚慢性JMV2959处理对本身的运动活性或VTA或NAc中GHS-R1A基因（Ghsr）的表达没有影响。此外，亚慢性胃饥饿素处理导致运动敏化。
虽然先前的研究已将胃饥饿素确定为一种食欲调节因子，但本研究与先前的研究共同表明，胃饥饿素信号传导调节啮齿动物中各种奖赏介导的行为。总的来说，这表明GHS-R1A可能是成瘾新治疗策略的关键靶点。
