Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Neuropsychopharmacology. 2018 Feb;43(3):617-626. doi: 10.1038/npp.2017.215. Epub 2017 Sep 12.
Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.
暴食症（BED）的特征是反复发作的过量食用美味食物和对食物线索的敏感性增加。暴食症患者表现出类似成瘾的症状，多巴胺系统可能是潜在的治疗靶点。临床安全的单胺稳定剂（-）-OSU6162（OSU6162）可恢复长期饮酒大鼠的多巴胺能功能障碍，并有望成为治疗酒精使用障碍的新方法。在这里，评估了 OSU6162 对非食物限制的雄性 Lister Hooded 大鼠的巧克力味蔗糖丸消耗性（暴食样进食）和食欲性（线索控制寻求）行为的影响。OSU6162 显著减少了巧克力味蔗糖丸的暴食样摄入，而不影响先前的谷物价。此外，OSU6162 在强化二级时间表下，显著减少了巧克力味蔗糖丸的线索控制寻求，而在奖励的给予和摄入之前，但不是之后，表明对激励动机过程有选择性作用。相比之下，多巴胺 D2/D3 受体拮抗剂氯丙嗪减少了巧克力味蔗糖丸的寻求，无论是在奖励摄入之前还是之后，并且减少了在更简单的寻求行为时间表下的反应。多巴胺 D1/5 受体拮抗剂 SCH23390 在任何测试的强化时间表下对仪器行为均无影响。最后，OSU6162 局部给药于伏隔核核心，但不是背外侧纹状体，选择性地减少了线索控制的蔗糖寻求。总之，目前的结果表明，OSU6162 减少了暴食样进食行为，并减轻了线索对美味食物寻求的影响。这表明 OSU6162 可能成为一种新的暴食症药物。
