Obesity Decreases Excitability of Putative Ventral Tegmental Area GABAergic Neurons

Palatable food has reinforcing effects on feeding and accelerates obesity. Alteration of food-related behavior in obesity may promote maintenance of obesity. The ventral tegmental area (VTA) of the midbrain is important for food reward. However, it is unknown whether activity of VTA neurons is altered in diet-induced obesity. In this study, we examined VTA neuronal activity using an electrophysiological technique in diet-induced obese mice. Male 4-week-old mice were fed a high-fat diet or a standard diet for 5-6 weeks. Mice fed a high-fat diet gained greater body weight with heavier visceral fat compared with those fed a standard diet. Brain slice preparations were obtained from the lean and obese mice. Spontaneous activity of VTA neurons was recorded extracellularly. We found a negative correlation between firing frequency (FF) and action potential (AP) current duration in lean and obese mice VTA neurons. VTA neurons were classified as group-1 neurons (FF <5.0 Hz and AP current duration >1.2 msec) or group-2 neurons (FF ≧5.0 Hz and AP current duration ≦1.2 msec). FF, AP current duration, and firing regularity of VTA group-1 neurons were similar between lean and obese mice. Obese mice VTA group-2 neurons had a lower FF and shorter AP current duration compared with lean mice. In conclusion, obesity minimally affects VTA group-1 neurons, which are presumed to be dopaminergic, but decreases excitability of VTA group-2 neurons, which are presumed to be GABAergic. This differential effect may contribute to the pathophysiology of reward-related feeding in obesity.