Modulation of food intake by the k opioid U-50,488H: evidence for an effect on satiation

The main goal of the present study was to test the hypothesis that the prophagic effect of the kappa opioid agonist U-50,488H (U50) is primarily due to an effect on satiation. In Experiment 1, the feeding effects of U50 (2.0 and 4.0 mg/kg, i.p.) was tested in animals with ad libitum access to ground food and to three sucrose solutions (1, 4, and 20%). In Experiment 2, a classical "one-bottle" test was utilized to test for the effect of U50 (4.0 mg/kg, i.p.) on the intake of five different sucrose solutions (1, 4, 16, 32, and 40%) over a 30-min period. Finally, in Experiment 3 we evaluated the effect of U50 (2.0, 4.0, and 6.0 mg/kg, i.p.) on extracellular dopamine (DA) concentration in the nucleus accumbens. In Experiment 1, U50 enhanced the intake of ground food but not of sucrose. In Experiment 2, U50 increased the intake of high concentration sucrose solutions whereas it decreased that of low concentration solutions. In Experiment 3, U50 produced a dose-dependent decrease in DA concentrations in the absence but not in the presence of food. The most likely explanation for the present results is that U50 enhances feeding by activating mechanisms that block satiety and satiation. In contrast, we found little evidence for an effect of U50 on palatability.