Dopamine D2 receptors mediate amylin's acute satiety effect

Abstract

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) D1- and D2-receptor antagonists on the anorectic effect of intraperitoneally injected amylin in rats fed a medium-fat (18% fat) diet. In 24-h food-deprived rats, pretreatment with the DA D2-receptor antagonist raclopride [100 μg/kg (0.2 μmol/kg) ip] significantly attenuated amylin's (5 μg/kg ip) anorectic effect, whereas raclopride alone had no effect 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 D2 receptor antagonist, sulpiride [50 mg/kg (154 μmol/kg) ip], similarly reduced amylin's satiety effect, whereas pretreatment with the DA D1-receptor antagonist SCH-23390 [10 μg/kg (0.03 μmol/kg) ip] did not influence amylin's effect. SCH-23390, however, completely blocked the anorexia induced by d-amphetamine (0.3 mg/kg ip). These results suggest that, under the present feeding conditions, the dopaminergic system mediates part of amylin's inhibitory effect on feeding in rats when administered intraperitoneally. This seems to involve DA D2 receptors but not D1 receptors.