Intracellular mechanisms of antidepressant drug action

The action of antidepressant drugs on monoamines such as norepinephrine and serotonin has been described for three decades. However, more-recent resea rch has looked beyond cell surface receptors to transductional cascades and gene expression. Antidepressant drug therapies seem to share several mecha nisms involved in either activating the adenylyl cyclase-protein kinase A c ascade or inhibiting the phospholipase C-protein kinase C mechanisms. These effects, ultimately, combine to regulate the expression of target genes. S everal specific genes are known to be activated or inhibited by antidepress ant therapies. Steady-state levels of mRNA for glucocorticoid and mineraloc orticoid receptors, brain-derived neurotrophic factor and its receptor trkB , and preproenkephalin are enhanced, whereas those for corticotropin-releas ing hormone, c-fos, N-methyl-D-aspartate receptor subunits, and nerve-growt h factor 1A are reduced. New molecular genetic methods for identifying diff erentially expressed genes will aid in the development of targets for wholl y new generations of antidepressant drug therapies.