Dopamine D-2 receptors mediate amylin's acute satiety effect

The anorectic effect of the pancreatic peptide amylin has been established in numerous studies. Here, we investigated the influence of a pretreatment with dopamine (DA) D-1- and D-2-receptor antagonists on the anorectic effec t of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) d iet. In 24-h food-deprived rats, pretreatment with the DA D-2-receptor anta gonist raclopride [100 mug/kg (0.2 mu mol/kg) ip] significantly attenuated amylin's (5 mug/kg ip) anorectic effect, whereas raclopride alone had no ef fect on food intake [i.e., food intakes 1 h after injection were (n = 12): NaCl/NaCl 7.3 +/- 0.5 g; NaCl/amylin 3.9 +/- 0.6; raclopride/NaCl 7.7 +/- 0 .7; raclopride/amylin 5.6 +/- 0.7]. Pretreatment with another DA D-2 recept or antagonist, sulpiride [50 mg/kg (154 mu mol/kg) ip], similarly reduced a mylin's satiety effect, whereas pretreatment with the DA D-1-receptor antag onist SCH-23390 [10 mug/kg (0.03 mu mol/kg) ip] did not influence amylin's effect. SCH-23390, however, completely blocked the anorexia induced by D-am phetamine (0.3 mg/kg ip). These results suggest that, under the present fee ding conditions, the dopaminergic system mediates part of amylin's inhibito ry effect on feeding in rats when administered intraperitoneally. This seem s to involve DA D-2 receptors but not D-1 receptors.