Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice.
Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice.
复制标题
合成迷幻剂 2,5-二甲氧基-4-碘苯丙胺 (DOI) 对雄性小鼠乙醇消耗和位置调节的影响。
DOI：
10.1007/s00213-019-05328-7
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发表时间：
2019
影响因子：
3.4
通讯作者：
Murnane,KevinS
中科院分区：
文献类型：
--
作者：
Oppong-Damoah,Aboagyewaah;Curry,KristenE;Blough,BruceE;Rice,KennerC;Murnane,KevinS
美国约有2000万成年人患有酒精使用障碍（AUD）。有临床和临床前数据表明迷幻药可能对AUD有益。目的探讨合成迷幻药2，5-二甲氧基-4-碘安非他明（DOI）对乙醇行为影响的影响。方法使用乙醇诱导的位置条件反射检查DOI的影响（1.8g/kg乙醇）和2瓶选择乙醇饮用（20%v/v），使用在5-羟色胺2A（5-HT 2A）受体依赖性头部抽动测定中产生最大反应的DOI剂量（3 mg/kg）。DOI和乙醇（3 g/kg）之间的相互作用进行了检查，使用乙醇引起的翻正反射程序和血液乙醇分析的损失。要检查psychedelics可能与乙醇相互作用的其他机制，我们确定是否DOI逆转乙醇诱导的一氧化氮释放在巨噬细胞，炎症的标志物。ResultsDOI显着衰减乙醇诱导的位置调节和乙醇饮用。DOI诱导的饮酒抑制依赖于5-HT 2A受体，对酒精的选择性超过对水的选择性，并且对高度酒精偏好的受试者具有选择性。DOI有没有明显的药代动力学与乙醇的相互作用，DOI减少乙醇诱导的一氧化氮release.ConclusionsOur研究结果表明，DOI块乙醇的位置条件和选择性地减少自愿乙醇消费。这可能与乙醇在大脑奖赏回路中的作用的调节、乙醇诱导的神经炎症或两者的组合有关。阐明致幻剂减弱乙醇作用的机制的其他研究将为AUD的病理生理学提供信息，并可能提供新的治疗选择。
RationaleApproximately 20 million adults in the USA have an alcohol use disorder (AUD). There are clinical and preclinical data suggesting that psychedelics may have benefits for AUD.ObjectiveTo investigate the effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on the behavioral effects of ethanol.MethodsThe effects of DOI were examined using ethanol-induced place conditioning (1.8 g/kg ethanol) and 2-bottle choice ethanol drinking (20%v/v), using a dose of DOI (3 mg/kg) that produced the maximal response in the serotonin 2A (5-HT2A) receptor-dependent head-twitch assay. Interactions between DOI and ethanol (3 g/kg) were examined using the ethanol-induced loss of righting reflex procedure and blood-ethanol analysis. To examine additional mechanisms by which psychedelics may interact with ethanol, we determined whether DOI reverses ethanol-induced nitric oxide release in macrophages, a marker of inflammation.ResultsDOI significantly attenuated ethanol-induced place conditioning and ethanol drinking. DOI-induced suppression of alcohol drinking depended upon 5-HT2Areceptors, was selective for alcohol over water, and was selective for high alcohol-preferring subjects. DOI had no apparent pharmacokinetic interactions with ethanol, and DOI reduced ethanol-induced nitric oxide release.ConclusionsOur findings demonstrate that DOI blocks ethanol place conditioning and selectively reduces voluntary ethanol consumption. This may be related to modulation of the effects of ethanol in the reward circuitry of the brain, ethanol-induced neuroinflammation, or a combination of both. Additional studies to elucidate the mechanisms through which psychedelics attenuate the effects of ethanol would inform the pathophysiology of AUD and potentially provide new treatment options.