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首页> 外文期刊>Journal of psychiatry & neuroscience: JPN >Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain
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Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

机译：长期服用多巴胺D3 / 2受体激动剂普拉克索可增加雄性大鼠前脑中的多巴胺和血清素神经传递

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Background: Long-term administration of the dopamine (DA) D2-like (D3/2) receptor agonist pramipexole (PPX) has been previously found to desensitize D2 autoreceptors, thereby allowing a normalization of the firing of DA neurons and serotonin (5-HT) 1A autoreceptors, permitting an enhancement of the spontaneous firing of 5-HT neurons. We hypothesized that PPX would increase overall DA and 5-HT neurotransmission in the forebrain as a result of these changes at the presynaptic level. Methods: Osmotic minipumps were implanted subcutaneously in male Sprague-Dawley rats, delivering PPX at a dose of 1 mg/kg/d for 14 days. The in vivo electrophysiologic microiontophoretic experiments were carried out in anesthetized rats. Results: The sensitivity of postsynaptic D2 receptors in the prefrontal cortex (PFC) remained unaltered following PPX administration, as indicated by the unchanged responsiveness to the microiontophoretic application of DA. Their tonic activation was, however, significantly increased by 104% compared with the control level. The sensitivity of postsynaptic 5-HT 1A receptors was not altered, as indicated by the unchanged responsiveness to the microiontophoretic application of 5-HT. Similar to other antidepressant treatments, long-term PPX administration enhanced the tonic activation of 5-HT 1A receptors on CA3 pyramidal neurons by 142% compared with the control level. Limitations: The assessment of DA and 5-HT neuronal tone was restricted to the PFC and the hippocampus, respectively. Conclusion: Chronic PPX administration led to a net enhancement in DA and 5-HT neuro transmission, as indicated by the increased tonic activation of postsynaptic D2 and 5-HT 1A receptors in forebrain structures.
机译：背景：先前已发现长期给予多巴胺（DA）D2样（D3 / 2）受体激动剂普拉克索（PPX）可使D2自身受体脱敏，从而使DA神经元和血清素的释放正常化（5- HT）1A自受体，可增强5-HT神经元的自发放电。我们假设，由于突触前水平的这些变化，PPX会增加前脑的整体DA和5-HT神经传递。方法：将渗透性微型泵皮下植入雄性Sprague-Dawley大鼠中，以1 mg / kg / d的剂量输送PPX，持续14天。在麻醉的大鼠中进行体内电生理微离子电渗疗法实验。结果：PPX给药后，前额叶皮层（PFC）中的突触后D2受体的敏感性保持不变，这表明DA对微离子电渗疗法的响应没有变化。然而，与对照组相比，它们的滋补激活明显增加了104％。突触后5-HT 1A受体的敏感性没有改变，如对5-HT的微离子电渗疗法的响应性不变。与其他抗抑郁药相似，长期服用PPX与对照相比，CA3锥体神经元上5-HT 1A受体的补强活化提高了142％。局限性：DA和5-HT神经元音调的评估分别限于PFC和海马。结论：慢性PPX给药导致DA和5-HT神经传递的净增强，正如前脑结构中突触后D2和5-HT 1A受体的强音激活所表明的。

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