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An amylin analogue attenuates alcohol-related behaviours in various animal models of alcohol use disorder.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-01-23 , DOI: 10.1038/s41386-019-0323-x
Aimilia Lydia Kalafateli 1 , Daniel Vallöf 1 , Giancarlo Colombo 2 , Irene Lorrai 2 , Paola Maccioni 2 , Elisabet Jerlhag 1
Affiliation  

Recent findings have identified salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, as a potential regulator of alcohol-induced activation of the mesolimbic dopamine system and alcohol consumption. Providing that the role of amylin signalling in alcohol-related behaviours remains unknown, the present experiments investigate the effect of sCT on these behaviours and the mechanisms involved. We showed that repeated sCT administration decreased alcohol and food intake in outbred rats. Moreover, single administration of the potent amylin receptor antagonist, AC187, increased short-term alcohol intake in outbred alcohol-consuming rats, but did not affect food intake. Acute administration of sCT prevented relapse-like drinking in the "alcohol deprivation effect" model in outbred alcohol-experienced rats. Additionally, acute sCT administration reduced operant oral alcohol self-administration (under the fixed ratio 4 schedule of reinforcement) in selectively bred Sardinian alcohol-preferring rats, while it did not alter operant self-administration (under the progressive ratio schedule of reinforcement) of a highly palatable chocolate-flavoured beverage in outbred rats. Lastly, we identified differential amylin receptor expression in high compared to low alcohol-consuming rats, as reflected by decreased calcitonin receptor and increased receptor activity modifying protein 1 expression in the nucleus accumbens (NAc) of high consumers. Collectively, our data suggest that amylin signalling, especially in the NAc, may contribute to reduction of various alcohol-related behaviours.

中文翻译:

胰岛淀粉样多肽类似物减弱了各种酒精使用障碍动物模型中与酒精有关的行为。

最近的发现已将鲑鱼降钙素(sCT),胰岛淀粉样多肽受体激动剂和内源性胰岛淀粉样多肽类似物确定为酒精诱导的中脑边缘多巴胺系统活化和酒精消耗的潜在调节剂。假设胰岛淀粉样多肽信号传导在酒精相关行为中的作用仍然未知,本实验研究了sCT对这些行为的影响以及所涉及的机制。我们表明,反复进行sCT给药可减少近交大鼠的酒精和食物摄入。此外,单用强力胰岛淀粉样受体拮抗剂AC187可以增加近距离饮酒大鼠的短期酒精摄入量,但不影响食物摄入。sCT的急性给药可防止在有过酒精经历的近交大鼠的“酒精剥夺效应”模型中出现类似复发的饮酒。此外,急性sCT给药减少了选择性繁殖撒丁岛偏爱酒精的大鼠的手术口服酒精自我给药(在固定比例4强化方案下),而并没有改变sardinian偏爱酒精的大鼠的手术自我给药(在强化逐步配比方案下)。一种在异种大鼠中非常可口的巧克力味饮料。最后,我们确定了与饮酒量低的大鼠相比胰岛淀粉样多肽受体表达的差异,这通过降低降钙素受体和增加受体活性来改变高消费群伏伏核(NAc)中蛋白1的表达所反映。总体而言,我们的数据表明胰岛淀粉样蛋白信号,尤其是在NAc中,可能有助于减少各种与酒精有关的行为。急性sCT给药在选择性繁殖撒丁岛偏爱酒精的大鼠中减少了手术口服酒精的自我给药(在固定比例4强化方案下),而并没有改变高度口服的口服酒精的自我给药(在强化的渐进比例方案下)。异种大鼠的可口巧克力味饮料。最后,我们确定了与饮酒量低的大鼠相比胰岛淀粉样多肽受体表达的差异,这通过降低降钙素受体和增加受体活性来改变高消费群伏伏核(NAc)中蛋白1的表达所反映。总体而言,我们的数据表明胰岛淀粉样蛋白信号,尤其是在NAc中,可能有助于减少各种与酒精有关的行为。急性sCT给药在选择性繁殖撒丁岛偏爱酒精的大鼠中减少了手术口服酒精的自我给药(在固定比例4强化方案下),而并没有改变高度口服的口服酒精的自我给药(在强化的渐进比例方案下)。异种大鼠的可口巧克力味饮料。最后,我们确定了与饮酒量低的大鼠相比胰岛淀粉样多肽受体表达的差异,这通过降低降钙素受体和增加受体活性来改变高消费群伏伏核(NAc)中蛋白1的表达所反映。总体而言,我们的数据表明胰岛淀粉样蛋白信号,尤其是在NAc中,可能有助于减少各种与酒精有关的行为。
更新日期:2019-01-26
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