McGavin Jacob J, Cochkanoff Nicholas L, Poole Emily I, Crosby Karen M
Biology Department, Mount Allison University, 63B York Street, Sackville, New Brunswick, E4L 1G7, Canada.
Biology Department, Mount Allison University, 63B York Street, Sackville, New Brunswick, E4L 1G7, Canada.
Neurosci Lett. 2019 Apr 17;698:27-32. doi: 10.1016/j.neulet.2019.01.008. Epub 2019 Jan 4.
The dorsomedial nucleus of the hypothalamus (DMH) is an important appetite regulatory center in the brain. In young rats, neural communication in the DMH is modulated by two interacting signals: endocannabinoids (eCBs) and nitric oxide (NO), both of which are known to modulate appetite. It remains unknown, however, whether eCBs and NO interact in the DMH to regulate food intake and body weight in young rats. We developed stereotaxic coordinates for the DMH in young, male Sprague-Dawley rats and conducted surgeries to implant bilateral guide cannulas for microinjection of vehicle, eCBs [2-arachidonylglycerol (2-AG) or anandamide]; NO (via the precursor l-arginine), or a combination of the two, with and without prior subcutaneous injections of drugs to block cannabinoid receptors or NO synthesis. Food intake and body weight of animals were measured two hours following the injection and brains were subsequently removed and sliced to verify placement of the cannulas relative to the DMH. Here we show that 2-AG, when administered in combination with l-arginine, significantly increased food intake and body weight, an effect that required type I cannabinoid receptors and NO synthesis. 2-AG and l-arginine had no effect on food intake or body weight when administered into the DMH independently. Anandamide also failed to affect these parameters when administered alone or with l-arginine. Together, these data suggest that 2-AG and NO interact in the DMH to increase food intake in young male rats and provide insight into a possible mechanism by which 2-AG increases appetite.
下丘脑背内侧核（DMH）是大脑中一个重要的食欲调节中心。在幼鼠中，DMH中的神经通讯由两种相互作用的信号调节：内源性大麻素（eCBs）和一氧化氮（NO），已知这两种物质都能调节食欲。然而，eCBs和NO是否在DMH中相互作用以调节幼鼠的食物摄入量和体重仍不清楚。我们为年轻的雄性Sprague-Dawley大鼠的DMH制定了立体定位坐标，并进行手术植入双侧引导套管，用于微量注射载体、eCBs [2-花生四烯酸甘油酯（2-AG）或花生四烯乙醇胺]；NO（通过前体L-精氨酸），或两者的组合，同时进行或不进行预先皮下注射药物以阻断大麻素受体或NO合成。在注射后两小时测量动物的食物摄入量和体重，随后取出大脑并切片，以验证套管相对于DMH的位置。在这里，我们表明，2-AG与L-精氨酸联合给药时，显著增加了食物摄入量和体重，这一效应需要I型大麻素受体和NO合成。单独向DMH注射2-AG和L-精氨酸时，对食物摄入量或体重没有影响。单独给药或与L-精氨酸联合给药时，花生四烯乙醇胺也未能影响这些参数。总之，这些数据表明，2-AG和NO在DMH中相互作用，以增加年轻雄性大鼠的食物摄入量，并为2-AG增加食欲的可能机制提供了见解。
