The effects of the kappa agonist PD-117302 on feeding behaviour in obese and lean Zucker rats

It has been suggested that super-sensitivity to, or overactivity of, endogenous opioid systems, particularly the dynorphin system, may be important in the development of obesity in the obese mouse (ob/ob). We have investigated the possibility that an increase in sensitivity to kappa agonists may also play a role in the development of obesity in another mutant rodent, the Zucker rat. The effects of the selective kappa agonist PD-117302 were investigated in both lean and obese Zucker rats. The lean Animals appeared to be more sensitive to the initial hyperphagic effects of PD-117302 than their obese littermates, although this initial hyperphagia was followed by a subsequent decrease in food intake so that by the end of the six-hour test period the Animals treated with PD-117302 had eaten less than the saline-treated controls. These changes in food intake were paralleled by increases and decreases in the duration of time spent feeding throughout the experiment. At the doses used in this study PD-117302 had no effect on locomotor activity. It is concluded that obese Zucker rats are not more sensitive to the hyperphagic effects of the kappa agonist (PD-117302 than their lean littermates and therefore it seems unlikely that increased sensitivity to an endogenous kappa opioid system plays a major part in the overeating and obesity observed in this strain of rat.