Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice
Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice
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DOI：
10.1016/j.drugalcdep.2011.01.010
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发表时间：
2011-09-01
影响因子：
4.2
通讯作者：
Engel, Jorgen A.
中科院分区：
文献类型：
--
作者：
Jerlhag, Elisabet;Engel, Jorgen A.
背景：促食欲肽 ghrelin 激活奖励系统，特别是胆碱能-多巴胺能奖励联系，这表明 ghrelin 可能会增加诸如食物寻找等动机行为的激励显着性。此外，涉及生长激素促分泌素受体 1A (GHS-R1A) 的中枢生长素释放肽信号传导是酒精、可卡因和安非他明的奖励特性所必需的，通过运动刺激、累积多巴胺释放和条件性位置偏好来测量。由于大脑中其他滥用药物（包括尼古丁）的目标回路包含此奖励链接，因此我们试图确定中枢生长素释放肽信号系统是否参与尼古丁激活该系统。方法：通过研究外周施用 GHS-R1A 拮抗剂（JMV2959）对尼古丁诱导的运动模拟、累积多巴胺释放和 结果：在本研究中，我们发现用 GHS-R1A 拮抗剂治疗的小鼠中，尼古丁增加运动活性、累积多巴胺释放和调节位置偏好的能力降低。结论：因此，GHS-R1A 似乎不仅是酒精、可卡因和安非他明诱导的奖赏所必需的，而且也是尼古丁诱导的奖赏所必需的。我们的数据表明，中央生长素释放肽信号系统可能构成治疗药物依赖的新的潜在靶点。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Background: The orexigenic peptide ghrelin activates the reward systems, specifically the cholinergic-dopaminergic reward link, suggesting that ghrelin may increase the incentive salience of motivated behaviours such as food seeking. Moreover, central ghrelin signalling, involving the growth hormone secretagogue receptor 1A (GHS-R1A), is required for the rewarding properties, as measured by locomotor stimulation, accumbal dopamine release and conditioned place preference, of alcohol, cocaine as well as amphetamine. As the target circuits for other drugs of abuse, including nicotine, in the brain includes this reward link, we sought to determine whether the central ghrelin signalling system is involved in nicotine's activation of this system.Methods: This was investigated by studying the effects of peripheral administration of a GHS-R1A antagonist (JMV2959) on the nicotine-induced locomotor simulation, accumbal dopamine release and conditioned place preference.Results: In the present study we found that the ability of nicotine to increase the locomotor activity, accumbal dopamine release and to condition place preference were reduced in mice treated with a GHS-R1A antagonist.Conclusion: Thus GHS-R1A appears to be required not only for alcohol, cocaine and amphetamine-induced reward, but also for reward induced by nicotine. Our data suggest that the central ghrelin signalling system may constitute a novel potential target for treatment of drug dependence. (C) 2011 Elsevier Ireland Ltd. All rights reserved.