Intracellular mechanisms of antidepressant drug action

Academic Article


  • The action of antidepressant drugs on monoamines such as norepinephrine and serotonin has been described for three decades. However, more-recent research has looked beyond cell surface receptors to transductional cascades and gene expression. Antidepressant drug therapies seem to share several mechanisms involved in either activating the adenylyl cyclase-protein kinase A cascade or inhibiting the phospholipase C-protein kinase C mechanisms. These effects, ultimately, combine to regulate the expression of target genes. Several specific genes are known to be activated or inhibited by antidepressant therapies. Steady-state levels of mRNA for glucocorticoid and mineralocorticoid receptors, brain-derived neurotrophic factor and its receptor trkB, and preproenkephalin are enhanced, whereas those for corticotropin-releasing hormone, c-fos, N-methyl-D-aspartate receptor subunits, and nerve-growth factor 1A are reduced. New molecular genetic methods for identifying differentially expressed genes will aid in the development of targets for wholly new generations of antidepressant drug therapies.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Shelton RC
  • Start Page

  • 161
  • End Page

  • 174
  • Volume

  • 8
  • Issue

  • 4