Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Neuroscience Institute, Section of Cagliari, National Research Council of Italy, Monserrato, CA, Italy.
Neuropsychopharmacology. 2019 May;44(6):1093-1102. doi: 10.1038/s41386-019-0323-x. Epub 2019 Jan 23.
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.
最近的研究结果表明，鲑鱼降钙素（sCT）作为内源性淀粉样素的一种类似物和淀粉样素受体激动剂，可能是调节酒精诱导的中脑边缘多巴胺系统激活和酒精消费的潜在调节剂。鉴于淀粉样素信号在与酒精相关的行为中的作用尚不清楚，本实验研究了 sCT 对这些行为的影响及其涉及的机制。我们发现，重复给予 sCT 可减少杂合大鼠的酒精和食物摄入量。此外，单次给予强效淀粉样素受体拮抗剂 AC187 可增加杂合酒精消耗大鼠的短期酒精摄入量，但不影响食物摄入量。急性给予 sCT 可预防杂合酒精经验大鼠的“酒精剥夺效应”模型中复发性饮酒。此外，急性 sCT 给药可减少选择性繁殖的撒丁岛酒精偏好大鼠的操作性口服酒精自我给药（强化比 4 方案），而不改变杂合大鼠的操作性自我给药（渐进比强化方案）高美味巧克力味饮料。最后，我们确定了高饮酒量和低饮酒量大鼠之间的差异淀粉样素受体表达，反映了在高消费大鼠的伏隔核（NAc）中降钙素受体表达减少和受体活性修饰蛋白 1 表达增加。总之，我们的数据表明，淀粉样素信号，特别是在 NAc 中，可能有助于减少各种与酒精相关的行为。
