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值得深思的是:饮食诱导的雄性大鼠决策能力损伤及 N-乙酰半胱氨酸的改善作用。

Food for thought: diet-induced impairments to decision-making and amelioration by N-acetylcysteine in male rats.

机构信息

School of Psychology, The University of New South Wales, Sydney, NSW, 2052, Australia.

Department of Physiology and Pharmacology, Hotchkiss Brain Institute, The University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada.

出版信息

Psychopharmacology (Berl). 2022 Nov;239(11):3495-3506. doi: 10.1007/s00213-022-06223-4. Epub 2022 Oct 11.

Abstract

RATIONALE

Attempts to lose weight often fail despite knowledge of the health risks associated with obesity and determined efforts. We previously showed that rodents fed an obesogenic diet displayed premature habitual behavioural control and weakened flexible decision-making based on the current value of outcomes produced by their behaviour. Thus, habitual control may contribute to failed attempts to modify eating behaviours.

OBJECTIVES

To examine the effects of an obesogenic diet on behavioural control and glutamate transmission in dorsal striatum regions and to assess the ability of N-acetylcysteine (NAC) to reverse deficits.

METHODS

Here, we examined diet-induced changes to decision-making and used in vitro electrophysiology to investigate the effects of diet on glutamate transmission within the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas that control goal-directed and habitual behaviours, respectively. We administered NAC in order to normalize glutamate release and tested whether this would restore goal-directed performance following an obesogenic diet.

RESULTS

We found that an obesogenic diet reduced sensitivity to outcome devaluation and increased glutamate release in the DMS, but not DLS. Administration of NAC restored goal-directed control and normalized mEPSCs in the DMS. Finally, NAC administered directly to the DMS was sufficient to reinstate sensitivity to outcome devaluation following an obesogenic diet.

CONCLUSIONS

These data indicate that obesogenic diets alter neural activity in the basal ganglia circuit responsible for goal-directed learning and control which leads to premature habitual control. While the effects of diet are numerous and widespread, normalization of glutamatergic activity in this circuit is sufficient for restoring goal-directed behaviour.

摘要

原理

尽管人们了解肥胖相关的健康风险,并付出了坚定的努力,但减肥的尝试往往还是会失败。我们之前的研究表明,喂食致肥胖饮食的啮齿动物表现出过早的习惯性行为控制,并削弱了基于其行为产生的当前结果价值的灵活决策能力。因此,习惯性控制可能会导致改变饮食行为的尝试失败。

目的

研究致肥胖饮食对背侧纹状体区域行为控制和谷氨酸传递的影响,并评估 N-乙酰半胱氨酸(NAC)逆转缺陷的能力。

方法

在这里,我们检查了饮食诱导的决策变化,并使用体外电生理学研究了饮食对背侧纹状体的背内侧(DMS)和背外侧(DLS)区域内谷氨酸传递的影响,这两个区域分别控制目标导向和习惯性行为。我们给予 NAC 以恢复谷氨酸释放,并测试在致肥胖饮食后这是否可以恢复目标导向行为。

结果

我们发现,致肥胖饮食降低了对结果贬值的敏感性,并增加了 DMS 中的谷氨酸释放,但在 DLS 中没有增加。给予 NAC 恢复了目标导向控制,并使 DMS 中的 mEPSC 正常化。最后,直接给予 DMS 的 NAC 足以在致肥胖饮食后恢复对结果贬值的敏感性。

结论

这些数据表明,致肥胖饮食改变了负责目标导向学习和控制的基底神经节回路中的神经活动,导致过早的习惯性控制。虽然饮食的影响是多方面的和广泛的,但该回路中谷氨酸能活动的正常化足以恢复目标导向行为。

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