Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats

Abstract

There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15-500 ng/side) or Arc (15-150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005-5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake.

Insulin dependent and independent normalization of blood glucose levels reduces the enhanced rewarding effects of nicotine in a rodent model of diabetes

“…For instance, ICV insulin administration decreases sucrose self-administration and CPP produced by palatable foods [49–51]. Furthermore, ICV and intra-VTA infusion of insulin decreases brain reward function [52,53], whereas direct administration of insulin into the nucleus accumbens leads to a concentration dependent change in dopamine release, with low to moderate concentrations increasing dopamine release, and high concentrations reducing dopamine levels [54]. …”

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards

“…Insulin receptors are found in the dopaminergic neurons in the ventral tegmental area (VTA) and striatum, which indicates its potential role in the reward system (27). Administration of insulin to the VTA in rodents is associated with decreased food intake, particularly highly palatable foods (28)(29)(30). Similarly, human imaging studies show that intranasal insulin increases satiety and suppresses food intake, potentially through enhancement of brain energy levels (31,32).…”

Enhanced vulnerability to tobacco use in persons with diabetes: A behavioral and neurobiological framework

“…For example, intra-cerebroventricular (ICV) administration of insulin reduces sucrose self-administration (Figlewicz et al, 2006;Sipols et al, 2000) and CPP produced by palatable food (Figlewicz et al, 2004). Also, ICV and intra-VTA infusions of insulin produce a decrease in brain reward function (Bruijnzeel et al, 2011;Carr et al, 2000). These findings suggest that insulin plays a modulatory role in the processing of natural rewards via homeostatic regulation of the mesolimbic circuitry.…”