The Florey Institute of Neuroscience and Mental Health, Mental Health Research Theme, Parkville/Melbourne, Victoria, Australia.
The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville/Melbourne, Victoria, Australia.
Eur J Neurosci. 2021 Aug;54(3):4877-4887. doi: 10.1111/ejn.15321. Epub 2021 Jun 17.
Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug-taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N-Acetylcysteine (NAC) is a cysteine pro-drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction-like behaviour towards highly palatable food in a rat model of diet-induced obesity. Adult male Sprague-Dawley rats were placed on a high-fat high-sugar diet for 8 weeks and then assigned to diet-induced obesity-prone (DIO) or diet-induced obesity-resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high-fat high-sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive-like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100 mg/kg, i.p.) for 14 days. By the end of the treatment period, lever-pressing by NAC-treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction-like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating.
一些肥胖个体表现出的强迫性进食形式与强迫性药物滥用行为具有相似之处，这是物质使用障碍的一个显著特征。这就提出了一种可能性，即药物成瘾治疗方法可能对治疗强迫性暴食有用。N-乙酰半胱氨酸（NAC）是一种半胱氨酸前体药物，在临床试验中已取得一定成功，可减少可卡因、大麻和香烟的使用，以及赌博和拔毛癖等强迫行为。我们评估了 NAC 对饮食诱导肥胖大鼠模型中对高美味食物成瘾样行为的影响。成年雄性 Sprague-Dawley 大鼠接受高脂肪高糖饮食 8 周，然后根据体重增加情况分为饮食诱导肥胖易感（DIO）或饮食诱导肥胖抵抗（DR）组。DIO 和 DR 大鼠接受操作性条件反射范式，即大鼠可以按压杠杆获取高脂肪高糖食物丸。这与信号奖励不可用的时期交替进行。在治疗前，与 DR 大鼠相比，DIO 大鼠在其巢箱中进食更多，在操作性会话中获得更多食物丸，并且在信号表示奖励不可用时响应更多（表明有强迫性觅食样）。与 DR 大鼠相比，DIO 大鼠在没有奖励的情况下持续响应的情况通过每天注射 NAC（100mg/kg，ip）14 天得到改善。在治疗期结束时，NAC 治疗的 DIO 大鼠的按压反应类似于 DR 大鼠。这些发现表明，NAC 减少了大鼠对食物的成瘾样行为，并支持该化合物在强迫性暴食中的潜在应用。
