INCREASE IN SEROTONIN-1A AUTORECEPTORS IN THE MIDBRAIN OF SUICIDE VICTIMS WITH MAJOR DEPRESSION - POSTMORTEM EVIDENCE FOR DECREASED SEROTONIN ACTIVITY

It has been hypothesized that a deficit in serotonin may be a crucial determinant in the pathophysiology of major depression. Serotonin-1A r eceptors are located on serotonin cell bodies in the midbrain dorsal r aphe (DR) nucleus, and the activation of these receptors inhibits the firing of serotonin neurons and diminishes the release of this neurotr ansmitter in the prefrontal cortex. Repeated treatment with some antid epressant medications desensitizes serotonin-1A receptors in the rat m idbrain. The present study determined whether the binding of [H-3]8-hy droxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotoni n-1A receptors, is altered in the midbrain of suicide victims with maj or depression, Radiolabeling of the serotonin-1A receptor in the DR va ried significantly along the rostral-to-caudal extent of the human mid brain. The binding of [H-3]8-OH-DPAT to serotonin-1A receptors was inc reased significantly in the midbrain DR of suicide victims with major depression as compared with psychiatrically normal control subjects, I n suicide victims with major depression, the increase in the binding o f [H-3]8-OH-DPAT to serotonin-1A receptors was detected in the entire DR and specifically localized to the dorsal and ventrolateral subnucle i. Enhanced radioligand binding of an agonist to inhibitory serotonin- 1A autoreceptors in the human DR provides pharmacological evidence to support the hypothesis of diminished activity of serotonin neurons in suicide victims with major depression.