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Activation of the amylin pathway modulates cocaine-induced activation of the mesolimbic dopamine system in male mice
Hormones and Behavior ( IF 3.5 ) Pub Date : 2020-11-10 , DOI: 10.1016/j.yhbeh.2020.104885
Aimilia Lydia Kalafateli 1 , Cajsa Aranäs 1 , Elisabet Jerlhag 1
Affiliation  

Besides food intake reduction, activation of the amylin pathway by salmon calcitonin (sCT), an amylin and calcitonin receptor agonist, inhibits alcohol-mediated behaviors in rodents. This involves brain areas processing reward, i.e. the laterodorsal (LDTg), ventral tegmental area (VTA) and nucleus accumbens (NAc). However, the effects of stimulation of the amylin pathway on behaviors caused by cocaine and the brain areas involved in these processes have not yet been investigated. We therefore explored in male mice, the effects of systemic administration of sCT on cocaine-induced locomotor stimulation, dopamine release in the NAc and cocaine reward, as well as reward-dependent memory of cocaine, in the conditioned place preference (CPP) paradigm. Moreover, the outcome of systemic sCT and cocaine co-administration for five days on locomotor activity was investigated. Lastly, the impact of sCT infusions into the LDTg, VTA, NAc shell or core on cocaine-evoked locomotor stimulation was explored. We found that sCT attenuated cocaine-induced locomotor stimulation and accumbal dopamine release, without altering cocaine's rewarding properties or reward-dependent memory retrieval in the CPP paradigm. Five days of cocaine administration caused locomotor stimulation in mice pre-treated with vehicle, but not with sCT. In mice infused with vehicle into the aforementioned reward-related areas, cocaine caused locomotor stimulation, a response that was not evident following sCT infusions. The current findings suggest a novel role for the amylinergic pathway as regulator of cocaine-evoked activation of the mesolimbic dopamine system, opening the way for the investigation of the amylin signalling in the modulation of other drugs of abuse.



中文翻译:

胰岛淀粉样多肽途径的激活调节可卡因诱导雄性小鼠中脑边缘多巴胺系统的激活

除减少食物摄入外,鲑鱼降钙素(sCT)(一种胰岛淀粉样多肽和降钙素受体激动剂)对胰岛淀粉样多肽途径的激活还抑制了啮齿动物中酒精介导的行为。这涉及大脑区域处理奖励,背嗅(LDTg),腹侧被盖区(VTA)和伏隔核(NAc)。然而,尚未研究刺激胰岛淀粉样多肽途径对可卡因和涉及这些过程的大脑区域引起的行为的影响。因此,我们在条件位置偏爱(CPP)范式中研究了雄性小鼠中sCT全身给药对可卡因诱导的运动刺激,NAc和可卡因奖励中多巴胺释放以及可卡因奖励依赖型记忆的影响。此外,研究了全身性sCT和可卡因共同给药五天对运动活动的影响。最后,探讨了将sCT输注到LDTg,VTA,NAc壳或核中对可卡因诱发的运动刺激的影响。我们发现,sCT减轻了可卡因诱导的运动刺激和多巴胺的释放,而没有改变CPP范式中可卡因的奖励特性或奖励依赖型记忆。给予可卡因五天后,用媒介物而非sCT预处理的小鼠引起运动刺激。在向上述奖励相关区域注入媒介物的小鼠中,可卡因引起运动刺激,这种反应在sCT输注后并不明显。目前的发现表明,淀粉样蛋白能途径作为可卡因诱发中脑边缘多巴胺系统活化的调节剂具有新的作用,为研究淀粉样蛋白信号传导在其他滥用药物的调制中的研究开辟了道路。CPP范例中的奖励性质或依赖奖励的记忆检索。给予可卡因五天后,用媒介物而非sCT预处理的小鼠引起运动刺激。在向上述奖励相关区域注入媒介物的小鼠中,可卡因引起运动刺激,这种反应在sCT输注后并不明显。目前的发现表明,淀粉样蛋白能途径作为可卡因诱发中脑边缘多巴胺系统活化的调节剂具有新的作用,为研究淀粉样蛋白信号传导在其他滥用药物的调制中的研究开辟了道路。CPP范例中的奖励性质或依赖奖励的记忆检索。给予可卡因五天后,用媒介物而非sCT预处理的小鼠引起运动刺激。在向上述奖励相关区域注入媒介物的小鼠中,可卡因引起运动刺激,这种反应在sCT输注后并不明显。目前的发现表明,淀粉样蛋白能途径作为可卡因诱发中脑边缘多巴胺系统活化的调节剂具有新的作用,为研究淀粉样蛋白信号传导在其他滥用药物的调制中的研究开辟了道路。sCT输注后反应不明显。目前的发现表明,淀粉样蛋白能途径作为可卡因诱发中脑边缘多巴胺系统活化的调节剂具有新的作用,为研究淀粉样蛋白信号传导在其他滥用药物的调制中的研究开辟了道路。sCT输注后反应不明显。目前的发现表明,淀粉样蛋白能途径作为可卡因诱发中脑边缘多巴胺系统活化的调节剂具有新的作用,为研究淀粉样蛋白信号传导在其他滥用药物的调制中的研究开辟了道路。

更新日期:2020-11-12
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