Head Mitchell A, McColl Laura K, Klockars Anica, Levine Allen S, Olszewski Pawel K
Faculty of Science and Engineering, University of Waikato, Hamilton 3214, New Zealand.
Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55113, USA.
J Clin Med. 2021 Dec 23;11(1):59. doi: 10.3390/jcm11010059.
A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.
最近的一项病例报告显示，在一名颅咽管瘤切除术后患有下丘脑性肥胖的青少年男性中，辅助使用催产素+纳曲酮（OT+NTX）治疗比单独使用OT能更显著地促进食欲减退和体重减轻。到目前为止，尚未有针对青春期实验动物的基础研究来探究OT+NTX对食欲的有益作用是否适用于未因手术导致暴饮暴食的青少年个体。因此，在此我们研究了低剂量的OT+NTX联合用药是否会急性影响青春期雄性大鼠在禁食后对能量密集型标准食物的摄入量、对能量密集型且美味的高脂肪高糖（HFHS）饮食的摄入量，或者对未禁食的热量稀释且美味的10%蔗糖溶液的摄入量。我们评估了OT+NTX是否会减少禁水后的饮水量或产生条件性味觉厌恶（CTA）。最后，通过使用c-Fos免疫反应性，我们确定了OT+NTX后与进食相关脑区的活动变化。我们发现，OT和NTX的亚阈值剂量单独使用时会减少由能量和适口性诱导的进食。在弓状核和下丘脑背内侧核中观察到了显著的c-Fos变化。OT+NTX的促食欲减退剂量并未抑制口渴大鼠的饮水量，也未引起CTA，这表明进食减少并非胃肠道不适或口渴处理变化的继发效应。我们得出结论，OT+NTX是一种能有效降低青春期雄性大鼠食欲的药物组合。
