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Glutamate—Hypothalamic-Pituitary-Adrenal Axis Interactions: Implications for Mood and Anxiety Disorders

Published online by Cambridge University Press:  07 November 2014

Sanjay J. Mathew ,
Jeremy D. Coplan ,
Eric L.P. Smith ,
Darryle D. Schoepp ,
Leonard A. Rosenblum  and
Jack M. Gorman
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Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a pathologic feature of certain mood and anxiety disorders that results in the increased production and secretion of corticotropin-releasing factor. There is increasing preclinical evidence that glutamate, an excitatory amino acid, plays an important role in the regulation of the HPA axis. Activation of glutamatergic projections to limbic structures such as the amygdala and brainstem structures such as the nucleus tractus solitarius is implicated in the stress response. There are laboratory and clinical suggestions that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists function as antidepressants, and that chronic antidepressant treatments have a significant impact on NMDA receptor function. Clinical investigations of glutamate antagonists in patients with mood and anxiety disorders are in their infancy, with a few reports suggesting the presence of mood-elevating properties. Ultimately, HPA axis modulators, serotonin-enhancing agents, and glutamate antagonists might serve to increase neurotropic factors in key brain regions for affective and anxiety regulation, providing a putative final common pathway.

Type
Feature Articles
Information
CNS Spectrums , Volume 6 , Issue 7: Novel Perspectives of Central CRF/HPA Axis Dysfunction , July 2001 , pp. 555 - 564
Copyright
Copyright © Cambridge University Press 2001

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