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The Journal of Neuroscience, September 15, 1998, 18(18):7394-7401

Increase in Serotonin-1A Autoreceptors in the Midbrain of Suicide Victims with Major DepressionPostmortem Evidence for Decreased Serotonin Activity

Craig A. Stockmeier^{1, 2}, Laura A. Shapiro¹, Ginny E. Dilley¹, Tamara N. Kolli¹, Lee Friedman¹, and Grazyna Rajkowska³

¹ Program in Basic and Clinical Neuroscience, Department of Psychiatry, and ² Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio 44106, and ³ Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi 39216

It has been hypothesized that a deficit in serotonin may be a crucial determinant in the pathophysiology of major depression. Serotonin-1A receptors are located on serotonin cell bodies in the midbrain dorsal raphe (DR) nucleus, and the activation of these receptors inhibits the firing of serotonin neurons and diminishes the release of this neurotransmitter in the prefrontal cortex. Repeated treatment with some antidepressant medications desensitizes serotonin-1A receptors in the rat midbrain. The present study determined whether the binding of [³H]8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors, is altered in the midbrain of suicide victims with major depression. Radiolabeling of the serotonin-1A receptor in the DR varied significantly along the rostral-to-caudal extent of the human midbrain. The binding of [³H]8-OH-DPAT to serotonin-1A receptors was increased significantly in the midbrain DR of suicide victims with major depression as compared with psychiatrically normal control subjects. In suicide victims with major depression, the increase in the binding of [³H]8-OH-DPAT to serotonin-1A receptors was detected in the entire DR and specifically localized to the dorsal and ventrolateral subnuclei. 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.

Key words: serotonin-1A receptors; dorsal raphe nucleus; major depression; suicide; postmortem brain

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18187394-08$05.00/0

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