Food restriction and leptin impact brain reward circuitry in lean and obese Zucker rats.

The rewarding effect produced by electrically stimulating certain sites in the lateral hypothalamus (LH) can be potentiated by food restriction and body weight loss in lean rats. Central leptin and insulin administration can suppress the rewarding impact of the stimulation. To determine whether there are additional peripheral signals that mediate the effect of weight loss on brain reward circuitry, we assessed changes in LH-self-stimulation following food restriction in the obese Zucker rat which develops resistance to circulating leptin and insulin. In addition, we examined the impact of acute food deprivation and leptin administration on LH self-stimulation in lean and obese Zucker rats. The number of brain stimulation rewards earned was measured over a range of LH stimulation frequencies that drove reward rates from zero to asymptotic levels. Restriction reduced frequency thresholds in a subset of lean and obese rats, whereas BSR was unaltered by acute food deprivation. Despite impairment in leptin signaling, intraventricular leptin (4 microg) increased thresholds in most lean and obese rats in which the rewarding effect was sensitive to restriction. These results show that brain reward circuitry in the obese Zucker rat is sensitive to weight loss and leptin.