DOWN-REGULATION OF BETA-ADRENERGIC AND DOPAMINERGIC RECEPTORS INDUCEDBY 2-PHENYLETHYLAMINE

1. The effects of chronic administration (28 days s.c. via Alzet osmot ic 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 recep tor subtypes have been measured in rat brain. H-3-CGP 12177 was used t o label beta-adrenoceptors; H-3-spiperone and H-3-SCH 23390 were used to label D2-like and D1-like receptors. 2. Total cortical beta-adrenoc eptor density was reduced by (-)-deprenyl but not 2-phenylethylamine a lone. Combined administration of 2-phenylethylamine and (-)-deprenyl r esulted in a significantly larger decrease than (-)-deprenyl alone. Su btype density analysis by competition experiments with ICI 89406 revea led that the (-)-deprenyl effect in cortex was due to a decrease in be ta1-adrenoceptor density. The combination of 2-phenylethylamine and (- )-deprenyl resulted in a significant decrease in both cortical beta1- and cortical beta2-adrenoceptors. Cerebellar beta-adrenoceptor density was not altered by the present drug treatments. The K(d) values for t otal beta-adrenoceptor densities and K(i) values for beta-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum. 3. Administration of 2-phenylethylamine and of (-)-dep renyl resulted in a decrease in the density of D1-like H-3-SCH 23390 b ut not D2-like H-3-spiperone binding to dopamine receptors in the stri atum. The effects of combined 2-phenylethylamine and (-)-deprenyl trea tment on H-3-SCH 23390 binding were additive. These drug treatments di d not alter K(d) values for these binding sites. 4. The down-regulatio n of catecholamine receptors following chronically increased availabil ity of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attr ibutable to a direct neuromodulatory action of 2-phenylethylamine on c atecholamine receptors. 5. The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO i nhibitor antidepressants on catecholamine receptor systems indicate th at this substrate for MAO may mediate some of the effects of MAO inhib itor antidepressants.