Decreased sensitivity of 5-HT(1D) receptors in melancholic depression.

Abstract

Brain serotonin (5-HT) function is abnormal in major depression, but the involvement of different 5-HT receptor subtypes has been little studied. The availability of selective ligands now makes it possible to test the sensitivity of 5-HT(1D) receptors in patients with depression. The aim of the study was to use the 5-HT(1D) receptor agonist, zolmitriptan, to test the sensitivity of 5-HT(1D) receptors in patients with depression before and after treatment with selective serotonin reuptake inhibitors (SSRIs). We measured the growth hormone response to zolmitriptan (5 mg orally) in patients with major depression before and after SSRI treatment. A matched sample of healthy subjects acted as a control group. The growth hormone response to zolmitriptan was blunted in patients with a melancholic depressive syndrome. SSRI treatment produced a marked reduction in zolmitriptan-induced growth hormone release. Patients with melancholic depression have impaired sensitivity of the post-synaptic 5-HT(1D) receptors that mediate growth hormone release. The reduction in 5-HT(1D) receptor sensitivity following SSRI treatment is probably an adaptive response to increased levels of synaptic 5-HT.