Studies in mice on the antagonism of (+)-amphetamine anorexia by α-methyl- p-tyrosine methyl ester HCl

Abstract

Experiments were carried out in mice to investigate the individual roles of dopamine and noradrenaline in both the production of (+)-amphetamine anorexia and in its antagonism by α-methyl- p-tyrosine methyl ester HCl. The anorexia resulting from (+)-amphetamine pretreatment (2 mg/kg, s.c.) was potentiated by intracerebroventricular injection of dopamine (8 μg) and noradrenaline (8 μg). Neither catecholamine, however, produced any anorectic effects when given alone at these dose levels. The anorexia produced by (+)-amphetamine was antagonised by α-methyl- p-tyrosine methyl ester HC1 (40–160 mg/kg, i.p.) and the submaximal antagonism at 80 mg/kg α-methyl- p-tyrosine was reversed by l-DOPA (40 and 80 mg/kg, i.p.) and by intracerebroventricular dopamine (4 and 8 μg). Noradrenaline, in intracerebroventricular doses of up to 8 μg, failed to produce this reversal. These results indicate that, although a role for both dopamine and noradrenaline may be implicated in the production of (+)-amphetamine anorexia and in its antagonism by α-methyl- p-tyrosme, the noradrenergic component is dependent upon a fully functional dopaminergic system.