Oxytocin Reduces Methylphenidate-Induced Dorsal Striatal Dopamine Release in Male Rhesus Macaques.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI:10.1093/ijnp/pyae056

Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio

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Abstract

Background: Oxytocin is being evaluated as a potential treatment for psychostimulant use disorders. It is unknown what effect oxytocin has on dopamine signaling in response to psychostimulants in brain regions such as the striatum where oxytocin and dopamine interact to process natural rewards. We investigated the effect of oxytocin on striatal dopamine release stimulated by methylphenidate whose mechanism of action is analogous to that of cocaine.

Methods: We conducted an [11C] raclopride positron emission tomography study to assess striatal dopamine release in male rhesus macaques treated with oxytocin (80 IU) (administered via the intranasal [N = 5] and intravenous [N = 6] routes) followed by methylphenidate/[11C] raclopride.

Results: Oxytocin delivered by both routes significantly reduced methylphenidate-stimulated dopamine release in the dorsal striatum (caudate/putamen). These effects were, in part, evidenced by a reduction in dorsal striatal [11C] raclopride binding potential (increased dopamine release) following oxytocin administration.

Conclusions: The results provide translational and mechanistic evidence for the potential role of oxytocin as a treatment for psychostimulant use disorders.

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催产素减少雄性恒河猴因甲基苯甲酸引起的背纹状体多巴胺释放。

背景：人们正在评估催产素作为精神兴奋剂使用障碍的潜在治疗方法。在纹状体等大脑区域，催产素和多巴胺相互作用来处理自然奖励，而催产素对多巴胺对精神兴奋剂的反应信号有什么影响尚不清楚。我们研究了催产素对哌甲酯刺激纹状体多巴胺释放的影响，其作用机制类似于可卡因。方法：我们通过[11C]雷氯pride正电子发射断层扫描研究，评估雄性恒河猴纹状体多巴胺释放：催产素（80 IU）[经鼻（N=5）和静脉（N=6）途径给药]后，哌甲酯/[11C]雷氯pride。结果：两种途径的催产素均显著减少了苯甲酸甲酯刺激的背纹状体（尾状核/壳核）多巴胺释放。这些影响在一定程度上可以通过催产素处理后背纹状体[11C]的raclopride结合电位降低（多巴胺释放增加）来证明。结论：本研究结果为催产素治疗精神兴奋剂使用障碍的潜在作用提供了翻译和机制证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.