Deep brain stimulation for treatment of obesity in rats

Abstract

Object Given the success of deep brain stimulation (DBS) in a variety of applications (for example, Parkinson disease and essential tremor), other indications for which there is currently little effective therapy are being evaluated for clinical use of DBS. Obesity may be one such indication. Studies of the control of feeding and appetite by neurosurgical lesioning have been completed previously. This study was conducted to test the authors' hypothesis that continuous bilateral stimulatory inhibition of the rat lateral hypothalamic nucleus (LH) would lead to significant and sustained decrease in food intake and subsequent weight loss. Methods Sixteen Sprague–Dawley rats were maintained on a high-fat diet. Daily food intake and weight gain were measured for 7 days, at which time the animals underwent stereotactic placement of 0.25-mm-diameter bipolar stimulating electrodes bilaterally in the LH. On postoperative Day 7, eight animals began to receive continuous stimulation of the LH. The remaining eight animals were left unstimulated as the control group. Individual animal weight, food intake, and water intake were monitored daily and continuously throughout the experiment until postoperative Day 24. Results There was a decreased rate of weight gain after surgery in all animals, but the unstimulated group recovered and resumed a linear weight gain curve. The stimulated group, however, failed to show weight gain and remained below the mean baseline for body mass. There was a significant weight loss between the stimulated and unstimulated groups. On postoperative Day 24, compared with the day of surgery (Day 0), the unstimulated group had a mean weight gain of 13.8%, whereas the stimulated group had a 2.3% weight loss on average (p = 0.001), yielding a 16.1% weight difference between the two groups. Conclusions Bilateral electrical stimulatory inhibition of the LH is effective in causing significant and sustained weight loss in rats.