Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference
Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference
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DOI：
10.1007/s00213-010-1907-7
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Engel, Jorgen A.
中科院分区：
文献类型：
--
作者：
Jerlhag, Elisabet;Egecioglu, Emil;Engel, Jorgen A.
最近，我们证明，基因或药理学抑制中枢生长激素释放肽信号系统，涉及生长激素促分泌素受体1A（GHS-R1 A），导致减少奖励的酒精。由于脑中生长激素释放肽的靶回路包括与奖励寻求行为密切相关的中脑边缘奖励通路，我们试图确定中枢生长激素释放肽信号系统是否是酒精以外的药物滥用的奖励所必需的，即可卡因或安非他明。我们发现，安非他明以及可卡因诱导的运动刺激和多巴胺释放减少在用GHS-R1 A拮抗剂。此外，GHS-R1 A拮抗剂也减弱了这些药物调节位置偏爱的能力，因此GHS-R1 A似乎不仅是酒精诱导的奖赏所必需的，而且也是精神兴奋剂药物诱导的奖赏所必需的。我们的数据表明，中央ghrelin信号系统构成了一个新的潜在目标，治疗成瘾行为，如药物依赖。
Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist.Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.