The effects of chronic electrical stimulation of the ventromedial hypothalamic nucleus in the rat.

Abstract

The purpose of this thesis was to examine more closely the changes in body growth following repeated exposure to ventromedial hypothalamic (VMH) stimulation. In the first experiment, body weight, food intake, and epididymal fat pad weight were evaluated in three groups of rats receiving either VMH stimulation, no stimulation (implanted control), or stimulation to areas adjacent to the VMH. Three hours of intermittent low level electrical stimulation were delivered three times per week for four weeks, after which the animals were monitored for another 10 days. There was a significant difference in the rate of weight gain between the VMH stimulated and the implanted control groups. The efficiency of food utilization was dramatically less for the first week of stimulation in the VMH group as compared to either of the control groups. There was no significant difference among groups in the amount of food eaten nor in their epididymal fat pad weights. These data indicate that chronic low level VMH stimulation results in a significantly reduced weight gain, but that the non-specific effects of electrical brain stimulation account for approximately 50% of this reduction. In the second experiment rats received only one week of stimulation (or three stimulation sessions) in order to determine if relatively little stimulation could produce a chronic, that is at least a four week, reduction in body weight. Consistent with the results of the first experiment, no statistically significant difference in the rate of weight gain was observed between the VMH and extra-VMH groups, although visual examination of the data shows that VMH stimulation gives rise to a shallower growth curve. Stimulation bound activity, which generally was associated with VMH sites, was the most important contributing factor to a reduction in weight gain. As a group, rats showing high levels of stimulation bound activity also showed a significant depression of food intake during the week of stimulation. Only two sites, one VMH and one extra-VMH, were accompanied by an increase in brown adipose tissue thermogenesis when core body temperature was maintained with a homeothermic blanket unit during stimulation. The data from the rats in both experiments were pooled and evaluated using a multidimensional scaling (MDS) analysis. The two dimensional MDS solution showed that rats with electrode placements within the VMH tended to gain less weight and eat less food than rats with electrode placements at similar anteroposterior coordinates, but outside the VMH. An increased lipolysis and/or decreased lipogenesis may contribute to the inhibition of weight gain observed in rats that receive VMH stimulation. A technology, such as the SA-2 small research animal body composition analyzer, that permits the monitoring of body composition over time would clarify this issue. (Abstract shortened by UMI.)