Activation of the amylin pathway modulates cocaine-induced activation of the mesolimbic dopamine system in male mice
Activation of the amylin pathway modulates cocaine-induced activation of the mesolimbic dopamine system in male mice
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DOI：
10.1016/j.yhbeh.2020.104885
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发表时间：
2021-01-01
影响因子：
3.5
通讯作者：
Jerlhag, Elisabet
中科院分区：
文献类型：
--
作者：
Kalafateli, Aimilia Lydia;Aranas, Cajsa;Jerlhag, Elisabet
除了减少食物摄入量之外，鲑鱼降钙素（sCT）（一种胰岛淀粉样多肽和降钙素受体激动剂）激活胰岛淀粉样多肽通路，还能抑制啮齿类动物的酒精介导的行为。这涉及处理奖励的大脑区域，即侧背区（LDTg）、腹侧被盖区（VTA）和伏隔核（NAc）。然而，刺激胰淀素途径对可卡因引起的行为以及参与这些过程的大脑区域的影响尚未得到研究。因此，我们在条件性位置偏好（CPP）范式中，在雄性小鼠中探索了全身施用 sCT 对可卡因诱导的运动刺激、NAc 中多巴胺释放和可卡因奖励以及可卡因奖励依赖性记忆的影响。此外，还研究了全身 sCT 和可卡因联合给药五天对运动活动的结果。最后，探讨了 sCT 输注至 LDTg、VTA、NAc 壳或核对可卡因诱发的运动刺激的影响。我们发现 sCT 减弱了可卡因诱导的运动刺激和累积多巴胺释放，而不改变可卡因的奖励特性或 CPP 范式中奖励依赖性记忆检索。给予可卡因五天后，用媒介物预处理的小鼠会产生运动刺激，但 sCT 则不会。在将载体注入上述奖励相关区域的小鼠中，可卡因引起运动刺激，这种反应在 sCT 输注后并不明显。目前的研究结果表明，胰岛淀粉样蛋白能途径作为可卡因诱发的中脑边缘多巴胺系统激活的调节剂具有新的作用，为研究胰岛淀粉样多肽信号传导在其他滥用药物调节中的研究开辟了道路。
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.