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 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.
Shelton
R C
RC
Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA.
D000928:Antidepressive Agents / Q000494:pharmacology*; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D000928:Antidepressive Agents; D012333:RNA, Messenger