The Effect of Kappa Opioid Receptor Antagonism on Energy Expenditure in the Obese Zucker Rat

Abstract

Food intake and, subsequently, body weight are influenced by endogenous opioids acting in the central nervous system. Agonists for the opioid receptor increase food intake, whereas antagonists reduce food intake. Body weight, however, is the result of food consumed and energy expended. Although much has been reported about the effect of opioid antagonism on food intake, less has been reported about its effect on energy expended. This study investigated the effect of selective antagonism of the kappa opioid receptor on food intake, body weight, and indicators of energy expenditure in male obese Zucker rats (n=10). Energy expenditure was measured by indirect calorimetry, whereas general activity and body temperature were measured by implanted radio frequency telemetry. Central administration of 30 µg of the kappa opioid receptor (KOR) antagonist norbinaltorphamine resulted in a significant 34% reduction in food intake (p =.001), a small reduction in body weight, a reduction in resting energy expenditure (p = .06), a reduction in respiratory quotient (p =.06), a 14% reduction in general activity, and a reduction in core body temperature. Reduction in body weight as a result of KOR inhibition in this study was related to a decrease in food intake but not related to an increase in energy expended or activity.