Neural Response to Catecholamine Depletion in Unmedicated Subjects With Major Depressive Disorder in Remission and Healthy Subjects

Abstract

The pathophysiologic mechanisms of major depressive disorder (MDD) consistently have been associated with altered catecholaminergic function, especially with decreased dopamine (DA) neurotransmission, by various sources of largely indirect evidence.1-4 An instructive paradigm for investigating the relationship between catecholaminergic function and depression more directly involves the mood response to catecholamine depletion (CD), achieved byadministering α-methylparatyrosine (AMPT),5,6 a competitive inhibitor of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase.7 Administration of AMPT decreases catecholamine transmission by depleting central DA and norepinephrine stores, evidenced by reduced concentrations of catecholamines and their metabolites in plasma, urine, and cerebrospinal fluid,8,9 and decreased occupancy of striatal DA receptors by DA.10