5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs?
Numerous observations support the notion that serotonin (5-hydroxytryptamine; 5-HT) and its multiple receptor subtypes are linked not only to the biological basis of depression, but also to the mechanism of action of antidepressant drugs. A general hypothesis of 5-HT receptor dysregulation in depression suggests that 5-HT1A receptors may be down-regulated, whereas 5-HT2 receptors may be up-regulated and display an inadequate ability to convert receptor occupancy by 5-HT into an adequate physiological response. Preclinical studies show that numerous antidepressants down-regulate both 5-HT1A and 5-HT2 receptors. Clinical studies using post mortem tissues, neuroendocrine probes, and platelet models also confirm that antidepressants down-regulate 5-HT receptors in depressed patients. In some cases this down-regulation correlates with measures of clinical antidepressant responsiveness. This correlation supports the hypothesis that down-regulation of 5-HT receptors, particularly the 1A and 2 subtypes, may be linked to the mechanism of action of numerous antidepressant drugs.
Department of Psychiatry, University of California, San Diego 92122.
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D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects*
D000928:Antidepressive Agents; D011985:Receptors, Serotonin