Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Neuropharmacology. 2012 Jul;63(1):76-86. doi: 10.1016/j.neuropharm.2012.02.005. Epub 2012 Feb 23.
The important role of dopamine (DA) in mediating feeding behavior and the positive reinforcing effects of some drugs is well recognized. Less widely studied is how feeding conditions might impact the sensitivity of drugs acting on DA systems. Food restriction, for example, has often been the focus of aging and longevity studies; however, other studies have demonstrated that mild food restriction markedly increases sensitivity to direct- and indirect-acting DA receptor agonists. Moreover, it is becoming clear that not only the amount of food, but the type of food, is an important factor in modifying the effects of drugs. Given the increased consumption of high fat and sugary foods, studies are exploring how consumption of highly palatable food impacts DA neurochemistry and the effects of drugs acting on these systems. For example, eating high fat chow increases sensitivity to some behavioral effects of direct- as well as indirect-acting DA receptor agonists. A compelling mechanistic possibility is that central DA pathways that mediate the effects of some drugs are regulated by one or more of the endocrine hormones (e.g. insulin) that undergo marked changes during food restriction or after consuming high fat or sugary foods. Although traditionally recognized as an important signaling molecule in regulating energy homeostasis, insulin can also regulate DA neurochemistry. Because direct- and indirect-acting DA receptor drugs are used therapeutically and some are abused, a better understanding of how food intake impacts response to these drugs would likely facilitate improved treatment of clinical disorders and provide information that would be relevant to the causes of vulnerability to abuse drugs. This article is part of a Special Issue entitled 'Central Control of Food Intake'.
多巴胺（DA）在介导摄食行为和某些药物的正性强化效应方面的重要作用已得到广泛认可。但摄食条件如何影响作用于 DA 系统的药物的敏感性，这方面的研究则相对较少。例如，食物限制通常是衰老和长寿研究的焦点；然而，其他研究表明，轻度食物限制可显著增加直接和间接作用的 DA 受体激动剂的敏感性。此外，越来越清楚的是，不仅食物的数量，而且食物的类型，也是调节药物作用的一个重要因素。鉴于高脂肪和高糖食物的消费增加，研究正在探索食用高美味食物如何影响 DA 神经化学和作用于这些系统的药物的效果。例如，食用高脂肪食物会增加直接作用和间接作用的 DA 受体激动剂的一些行为效应的敏感性。一种引人注目的机制可能性是，介导某些药物作用的中枢 DA 途径可能受到一种或多种内分泌激素（如胰岛素）的调节，这些激素在食物限制或食用高脂肪或高糖食物后会发生明显变化。尽管胰岛素传统上被认为是调节能量平衡的重要信号分子，但它也可以调节 DA 神经化学。由于直接和间接作用的 DA 受体药物被用于治疗，并且一些被滥用，因此，更好地了解食物摄入如何影响对这些药物的反应，可能有助于改善对临床疾病的治疗，并提供与滥用药物易感性有关的信息。本文是题为“摄食的中枢控制”的特刊的一部分。
