Oxytocin decreases alcohol self-administration in male baboons

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-09-11 DOI:10.1038/s41398-024-03076-7
Mary R. Lee, Catherine F. Moore, Elise M. Weerts
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Abstract

The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.

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催产素可降低雄性狒狒的酒精自我摄取量
神经激素催产素(OT)已被提议作为治疗酒精和尼古丁使用障碍的一种方法。本研究旨在探讨在 6 小时酒精摄入程序下,静脉注射催产素是否会降低非人灵长类动物的酒精口服自我给药量和消耗量,以及在 6 小时同时摄入条件下,酒精和尼古丁(静脉注射)自我给药量是否会降低。研究对象是五只雄性狒狒(Papio anubis),它们在每次饮酒的固定比例为 3(FR3)的安排下,在 6 小时的时间内自我口服酒精(4% w/v)。确定酒精自我给药的基线水平后,开始进行 OT 治疗。在连续 5 天的 6 小时饮酒过程中,分别在饮酒前和饮酒中间注射单剂量催产素(20、40、80、120 IU,静脉注射)或其载体(生理盐水)(催产素总剂量分别为 40、80、160、240 IU/天)。每个 5 天的治疗结束后,在下一个 5 天的催产素治疗前重新建立酒精自我给药的基线水平。此外,我们还对其中 3 只狒狒进行了 OT 对同时进行酒精和静脉注射尼古丁自我给药的影响研究,这 3 只狒狒在 6 小时的治疗过程中同时使用酒精和尼古丁,每种药物的治疗时间安排为 FR3。建立自我给药基线和完成为期 5 天的 OT 治疗与仅酒精研究相同。与安慰剂相比,使用 OT 后酒精消耗量明显减少。经事后分析,在校正多重比较后,40 和 80 IU 剂量的 OT 比安慰剂显著降低了酒精消耗量,而且在每个 5 天的治疗期内,酒精消耗量没有显著变化。从质量上讲,在每只狒狒中,至少有一种剂量的 OT 能减少酒精和尼古丁的同时摄入。这些结果凸显了催产素作为治疗酒精使用障碍以及可能的尼古丁联合使用的一种疗法的潜力。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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