Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation.
Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation.
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DOI：
10.1093/ijnp/pyw113
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发表时间：
2017-05-01
期刊：
影响因子：
--
通讯作者：
Ikeda K
中科院分区：
文献类型：
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作者：
Ide S;Takahashi T;Takamatsu Y;Uhl GR;Niki H;Sora I;Ikeda K
阿片和多巴胺系统在奖赏中起着至关重要的作用。由这两个系统介导的奖励神经机制的相似性和差异在很大程度上仍然未知。因此，在本研究中，我们研究了μ-阿片受体敲除小鼠和多巴胺转运蛋白敲除小鼠（阿片和多巴胺系统中的重要分子）中奖赏功能的差异。将电极植入小鼠右侧下丘脑（1小时）。然后训练小鼠将其口鼻放入头部浸入室的孔中进行颅内电刺激，并评估基因敲除的影响。阿片和多巴胺系统之间的奖励功能的显着差异。μ-阿片受体敲除小鼠表现出增强的颅内电刺激，其诱导多巴胺释放。在悬尾试验和水车试验中，它们在“绝望”条件下也表现出更大的运动性。相比之下，多巴胺转运蛋白敲除小鼠即使在需要更积极的努力来获得奖励时也能保持颅内电刺激反应。μ-阿片受体或多巴胺转运蛋白的缺失并不导致颅内电刺激反应性的缺失，而是差异性地改变了颅内电刺激反应性。目前在μ-阿片受体敲除小鼠中的结果与μ-阿片受体在与颅内电刺激相关的正性激励动机和与抑郁状态相关的负性激励动机中的抑制性参与一致。相反，多巴胺转运蛋白基因敲除小鼠的结果与多巴胺转运蛋白参与积极激励动机，特别是其持久性是一致的。在μ-阿片受体和多巴胺转运蛋白敲除小鼠中颅内电刺激的差异强调了奖励的多维性质。
Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these 2 systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout mice and dopamine transporter knockout mice, important molecules in the opioid and dopamine systems. Mice were implanted with electrodes into the right lateral hypothalamus (l hour). Mice were then trained to put their muzzle into the hole in the head-dipping chamber for intracranial electrical stimulation, and the influences of gene knockout were assessed. Significant differences are observed between opioid and dopamine systems in reward function. µ-Opioid receptor knockout mice exhibited enhanced intracranial electrical stimulation, which induced dopamine release. They also exhibited greater motility under conditions of “despair” in both the tail suspension test and water wheel test. In contrast, dopamine transporter knockout mice maintained intracranial electrical stimulation responding even when more active efforts were required to obtain the reward. The absence of µ-opioid receptor or dopamine transporter did not lead to the absence of intracranial electrical stimulation responsiveness but rather differentially altered it. The present results in µ-opioid receptor knockout mice are consistent with the suppressive involvement of µ-opioid receptors in both positive incentive motivation associated with intracranial electrical stimulation and negative incentive motivation associated with depressive states. In contrast, the results in dopamine transporter knockout mice are consistent with the involvement of dopamine transporters in positive incentive motivation, especially its persistence. Differences in intracranial electrical stimulation in µ-opioid receptor and dopamine transporter knockout mice underscore the multidimensional nature of reward.