2-PHENYLETHYLAMINE-INDUCED CHANGES IN CATECHOLAMINE RECEPTOR DENSITY - IMPLICATIONS FOR ANTIDEPRESSANT DRUG-ACTION

It is now established that (1) concentrations of 2-phenylethylamine (P EA) are greatly increased in brain following administration of monoami ne oxidase inhibitor (MAOI) antidepressants; (2) PEA is a metabolite o f the MAOI antidepressant phenelzine; and (3) PEA may be a neuromodula tor of catecholamine activity. On the basis of these observations, the effects of long term increases in brain PEA on catecholamine receptor s have been assessed. Both PEA and antidepressants induced a reduction in the behavioural response to the beta2 adrenoceptor agonist salbuta mol. Radioligand binding measurements revealed that 28 day administrat ion of PEA in combination with the type B MAOI (-)-deprenyl results in a decrease in the density of beta1 adrenoceptors but not beta2 adreno ceptors in rat cerebral cortex and cerebellum. (-)-Deprenyl alone also induced a significant decrease in beta1-adrenoceptors but when PEA wa s added to this treatment there was a further decrease in beta1-adreno ceptor density. Only changes in beta1 adrenoceptor density were eviden t following day administration of MAOI antidepressants. PEA also induc ed a decrease in the density of D1-like dopamine (DA) receptors in the rat striatum. MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors. These data are discussed in terms of a possible role of PEA-catecholamine interactions in antidepr essant drug action.