部分多巴胺转运体缺乏症雄性大鼠的乙醇摄入模式

IF 2.4 4区 心理学 Q2 BEHAVIORAL SCIENCES
L. B. Kuiper, J. B. Roberts, P. M. Estave, D. Leo, R. R. Gainetdinov, S. R. Jones
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引用次数: 0

摘要

中叶多巴胺信号在酒精和药物使用障碍以及焦虑和抑郁等合并症中起着重要作用。越来越多的证据表明,饮酒受多巴胺转运体(DAT)功能的调节,DAT能严格调节细胞外多巴胺的浓度。本研究使用了Wistar Han背景的成年雄性大鼠(DAT+/+)和部分DAT缺失的大鼠(DAT+/-)。首先,我们使用快速扫描环形伏安法检测了来自乙醇免疫受试者的含有脑核核心的脑切片,在DAT+/-大鼠体内测得了更高的诱发多巴胺浓度和更慢的多巴胺再摄取速度,这与多巴胺信号传导增加一致。接下来,我们使用间歇性双瓶选择范式(20% v/v 乙醇与水)测量了大鼠5周的乙醇饮用量。DAT+/-大鼠在乙醇供应初期(前30分钟)自愿摄入的乙醇较少,尤其是在较长时间的剥夺后。此外,DAT+/-雄性大鼠消耗的掺有苦味剂奎宁的乙醇更少。这些研究结果表明,部分阻断DAT和同时增加大脑多巴胺水平有可能减少饮酒和改善酒精使用障碍(AUD)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

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来源期刊
Genes Brain and Behavior
Genes Brain and Behavior 医学-行为科学
CiteScore
6.80
自引率
4.00%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.
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