2-Phenylethylamine-induced changes in catecholamine receptor density: implications for antidepressant drug action.
It is now established that (1) concentrations of 2-phenylethylamine (PEA) are greatly increased in brain following administration of monoamine oxidase inhibitor (MAOI) antidepressants; (2) PEA is a metabolite of the MAOI antidepressant phenelzine; and (3) PEA may be a neuromodulator of catecholamine activity. On the basis of these observations, the effects of long term increases in brain PEA on catecholamine receptors have been assessed. Both PEA and antidepressants induced a reduction in the behavioural response to the beta 2 adrenoceptor agonist salbutamol. Radioligand binding measurements revealed that 28 day administration of PEA in combination with the type B MAOI (-)-deprenyl results in a decrease in the density of beta 1 adrenoceptors but not beta 2 adrenoceptors in rat cerebral cortex and cerebellum. (-)-Deprenyl alone also induced a significant decrease in beta 1-adrenoceptors but when PEA was added to this treatment there was a further decrease in beta 1-adrenoceptor density. Only changes in beta 1 adrenoceptor density were evident following 28 day administration of MAOI antidepressants. PEA also induced 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 antidepressant drug action.
Paetsch
P R
PR
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Greenshaw
A J
AJ
D000818:Animals; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D010649:Phenylalanine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D017983:Receptors, Catecholamine / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D018377:Neurotransmitter Agents; D010627:Phenethylamines; D011619:Psychotropic Drugs; D011943:Receptors, Adrenergic, beta; D017983:Receptors, Catecholamine; D011954:Receptors, Dopamine; C029261:phenethylamine; D010649:Phenylalanine