The kappa agonists PD117302 and U50488 produce a biphasic effect on 24 hour food intake in the rat

The effects of the selective kappa opioid receptor agonists PD117302 [(+/-)trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl-]benzo-[b]- thiophene-4-acetamide] and U50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide) were investigated on food intake in non-deprived rats over a 24 hr period following subcutaneous administration. At doses of 2.5 mg/kg and 5 mg/kg, both PD117302 and U50488 initially increased food intake. Between 6-24 hr, however, PD117302 (2.5-10 mg/kg) and U50488 (2.5 mg/kg and 5 mg/kg) caused a reduction in food intake. The largest doses of PD117302 and U50488 also reduced total 24 hr food intake. The reduction in food intake produced by PD117302 (5 mg/kg) was selective, since the intake of water was not affected. It is concluded that the kappa agonists PD117302 and U50488 produce a biphasic effect on 24 hr food intake, with an initial hyperphagia followed by a decrease in food intake.