中枢给药的生长激素分泌受体拮抗剂 DLys 会降低雄性小鼠的酒精摄入量和偏好。

IF 1.6 4区 医学 Q4 NEUROSCIENCES Neuroreport Pub Date : 2024-10-02 Epub Date: 2024-07-22 DOI:10.1097/WNR.0000000000002078
Rani S Richardson, Juan L Gomez, Leandro F Vendruscolo, Lorenzo Leggio, Andrey E Ryabinin
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引用次数: 0

摘要

酒精使用障碍(AUD)是一个非常普遍的公共健康问题。胃泌素系统已被确定为治疗 AUD 的潜在靶点。以前的研究表明,全身给药生长激素分泌受体(GHSR)拮抗剂 DLys 可以减少雄性小鼠的酒精摄入量和酒精偏好。然而,目前还不清楚是中枢还是外周 GHSR 介导了这些效应。我们假设酒精消费是由中枢 GHSRs 驱动的,并通过测试中枢给药 DLys 的效果来解决这一假设。雄性 C57BL/6J 小鼠在双瓶选择程序(10% 乙醇与水)中饮酒。连续7天脑室内注射DLys(2 nmol),以检测酒精摄入量和偏好。DLys可降低酒精摄入量和偏好,但对食物摄入量没有影响。对酒精摄入量和偏好的影响在多次给药后仍持续存在,表明对 DLys 的作用缺乏耐受性。这些结果表明,中枢给药 DLys 足以减少饮酒,而且脑室内给药 DLys 在多次给药后仍然有效。此外,这项研究还表明,脑室内给药 DLys 对酒精的影响是特定的,不会泛化到其他热量驱动的行为中。
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Centrally administered growth hormone secretagogue receptor antagonist DLys decreases alcohol intake and preference in male mice.

Alcohol use disorder (AUD) is a highly prevalent public health problem. The ghrelin system has been identified as a potential target for therapeutic intervention for AUD. Previous work showed that systemic administration of the growth hormone secretagogue receptor (GHSR) antagonist DLys reduced alcohol intake and preference in male mice. Yet, it is unclear whether central or peripheral GHSRs mediated these effects. We hypothesized that alcohol consumption is driven by central GHSRs and addressed this hypothesis by testing the effects of central administration of DLys. Male C57BL/6J mice consumed alcohol in a two-bottle choice procedure (10% ethanol versus water). DLys (2 nmol) was administered intracerebroventricularly for 7 days to examine alcohol intake and preference. DLys decreased alcohol intake and preference but had no effect on food intake. The effects on alcohol intake and preference persisted after several administrations, indicating lack of tolerance to DLys' effects. These results suggest that central administration of DLys is sufficient to reduce alcohol drinking and that DLys remains effective after several administrations when given intracerebroventricularly. Moreover, this work suggests that the effects of intracerebroventricularly administered DLys are specific to alcohol and do not generalize to other calorie-driven behaviors.

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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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