Differential actions of dopamine receptor antagonism in rats upon food intake elicited by either mercaptoacetate or exposure to a palatable high-fat diet

Selective dopamine receptor antagonists have been shown to reduce food inta ke of rats under such regulatory challenge conditions as food deprivation a nd 2-deoxy-D-glucose-induced glucoprivation, and under such palatable condi tions as acute exposure to sucrose solutions. Food intake is increased foll owing either pretreatment with the free fatty acid oxidation inhibitor, mer captoacetate (MA), or acute exposure to a palatable high-fat source. The pr esent study examined whether equimolar doses (50-800 nmol/kg, sc) of either the selective D-1 receptor antagonist, SCH23390, or the selective D-2 rece ptor antagonist, raclopride, would alter food intake elicited by either MA (70 mg/kg, ip) or acute exposure to a high-fat diet (67% ground rat chow, 3 3% vegetable shortening). SCH23390 significantly and dose-dependently reduc ed MA-induced feeding with the two higher (400 and 800 nmol/kg) doses elimi nating this response after the first 2 h and the two lower (50 and 200 nmol /kg) doses preventing the occurrence of significant MA-induced feeding. Rac lopride eliminated MA-induced feeding at the highest dose, and produced dos e-dependent reductions at lower doses. A different pattern of dopamine anta gonist effects emerged for high-fat intake. The identical dose range of SCH 23390 failed to alter high-fat intake. In contrast, whereas the highest (80 0 nmol/kg) dose of raclopride significantly reduced high-fat intake after 1 h, the middle (200 and 400 nmol/kg) doses of raclopride significantly incr eased high-fat intake after 2 h. These data are discussed in terms of the m odulatory actions of dopamine upon food intake, of the differential actions of dopamine receptor subtypes upon intake under challenge and palatable co nditions, and of the potential participation of presynaptic and postsynapti c receptor populations in these responses. (C) 2001 Elsevier Science Inc. A ll rights reserved.