The effect of opioid antagonism on food intake behavior and body weight in a biobehavioral model of obese binge eating.

The obese Zucker rat (OZR) exhibits a hyperphagic eating pattern similar to the obese binge eater. Dynorphin, an endogenous agonist of the kappa receptor, is associated with regulation offood intake. Lessened sensitivity to opioid antagonists and/or increased central dynorphin levels may contribute to the hyperphagic eating pattern observed in the OZR. This study examined the temporal effect of a single intracerebroventricular (ICV) dose of nor-binaltorphimine (NBNI), a specific and long-lasting kappa opioid antagonist, on food intake, body weight, and satiety measures (meal size and the shape of the cumulative food intake curve [CFIC]) in adult male OZRs. Analysis of individual subjects revealed a differential response to opioid antagonism with respect to weight loss, reduction in food intake, and change in the slope of the CFIC, with some responding and others responding poorly. Repeated-measures analysis of variance showed a significant decrease in body weight (P = 0.001) and food intake (P = 0.03) in responders compared to poor responders and controls. Satiation was influenced to a greater extent in responders, who showed a significant reduction in meal size and a greater change in the CFICfor the largest meal of the day toward a pattern of satiation. These data suggest that a differential response to chronic opioid antagonism may exist in the OZR.