Abstract
1. The effects of chronic administration (28 days s.c. via Alzet osmotic minipumps) of 2-phenylethylamine.HCl (10 mg kg-1 per day) and/or (-)-deprenyl.HCl (1 mg kg-1 per day) on dopamine and noradrenaline receptor subtypes have been measured in rat brain. 3H-CGP 12177 was used to label beta-adrenoceptors; 3H-spiperone and 3H-SCH 23390 were used to label D2-like and D1-like receptors. 2. Total cortical beta-adrenoceptor density was reduced by (-)-deprenyl but not 2-phenylethylamine alone. Combined administration of 2-phenylethylamine and (-)-deprenyl resulted in a significantly larger decrease than (-)-deprenyl alone. Subtype density analysis by competition experiments with ICI 89406 revealed that the (-)-deprenyl effect in cortex was due to a decrease in beta 1-adrenoceptor density. The combination of 2-phenylethylamine and (-)-deprenyl resulted in a significant decrease in both cortical beta 1- and cortical beta 2-adrenoceptors. Cerebellar beta-adrenoceptor density was not altered by the present drug treatments. The Kd values for total beta-adrenoceptor densities and Ki values for beta-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum. 3. Administration of 2-phenylethylamine and of (-)-deprenyl resulted in a decrease in the density of D1-like 3H-SCH 23390 but not D2-like 3H-spiperone binding to dopamine receptors in the striatum. The effects of combined 2-phenylethylamine and (-)-deprenyl treatment on 3H-SCH 23390 binding were additive. These drug treatments did not alter Kd values for these binding sites. 4. The down-regulation of catecholamine receptors following chronically increased availability of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attributable to a direct neuromodulatory action of 2-phenylethylamine on catecholamine receptors. 5. The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO inhibitor antidepressants on catecholamine receptor systems indicate that this substrate for MAO may mediate some of the effects of MAO inhibitor antidepressants.