Antidepressants and Hypothalamic-Pituitary-Adrenocortical Regulation

I. Introduction PAST studies of antidepressants have focused almost exclusively on their effects on the metabolism and receptors of monoamine neurotransmitters in various brain regions. These studies have been extended to the molecular effects of antidepressants and have led to a profoundly expanded understanding of their actions in the central nervous system. For example, long-term administration of antidepressants decreases the expression of tyrosine hydroxylase, down-regulates cAMP-dependent protein kinase, modulates the mRNA expression of central β-adrenoceptors and serotonin (5-HT) receptors, and alters the functional activity of specific G protein subunits and adenylyl cyclase (1). Taken together, these and many other recent observations clearly indicate that antidepressants interfere not only with the production and release of catecholamines and indolamines but also with the signal transduction of those neurotransmitters that have long been implicated in the pathogenesis and treatment of depression.