Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-25T10:01:54.188Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Holsboer, F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23:477–501.CrossRefGoogle ScholarPubMed
2. Heim, C, Newport, DJ, Heit, S, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000;284:592–597.CrossRefGoogle ScholarPubMed
3. Coplan, JD, Andrews, MW, Rosenblum, LA, et al. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proc Natl Acad Sci U S A. 1996;93:1619–1623.CrossRefGoogle Scholar
4. Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000;57:925–935.CrossRefGoogle Scholar
5. Lopez, JF, Akil, H, Watson, SJ. Neural circuits mediating stress. Biol Psychiatry. 1999;46:1461–1471.CrossRefGoogle ScholarPubMed
6. Skolnick, P. Antidepressants for the new millennium. Eur J Pharmacol. 1999;375;31–40.Google Scholar
7. Cotman, CW, Kahle, JS, Miller, SE, et al. Excitatory amino acid neurotransmission. In: Bloom, FE, Kupfer, DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven; 1995:75–85.Google Scholar
8. Krystal, JH, D'Souza, CD, Petrakis, IL, et al. NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harvard Rev Psychiatry. 1999;7:125–143.CrossRefGoogle ScholarPubMed
9. Marek, GJ, Aghajanian, GK. Excitation of interneurons in piriform cortex by 5-hydroxytryptamine (5-HT): blockade by MDL 100,907, a highly selective 5-HT2A antagonist. Eur J Pharmacol. 1994;259:137–141.CrossRefGoogle Scholar
10. Maragakis, NJ, Rothstein, JD. Glutamate transporters in neurologic disease. Arch Neurol. 2001;58:365–370.CrossRefGoogle ScholarPubMed
11. Brauner-Osborne, H, Egebjerb, J, Nielsen, EO, et al. Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000;43:2609–2645.CrossRefGoogle ScholarPubMed
12. Gabr, RW, Birkle, DL, Azzaro, AJ. Stimulation of the amygdala by glutamate facilitates corticotropin-releasing factor release from the median eminence and activation of the hypothalamic-pituitary-adrenal axis in stressed rats. Neuroendocrinology. 1995;62:333–339.CrossRefGoogle ScholarPubMed
13. Crafty, MS, Birkle, DL. N-methyl-D-aspartate (NMDA)-mediated corticotropin-releasing factor (CRF) release in cultured rat amygdala neurons. Peptides. 1999;20:93–100.Google Scholar
14. Feldman, S, Weidenfeld, J. Hypothalamic mechanisms mediating glutamate effects on the hypothalamie-pituitary-adrenocortical axis. J Neural Transm. 1997:104:633–642.CrossRefGoogle ScholarPubMed
15. Singewald, N, Zhou, GY, Chen, F, et al. Corticotropin-releasing factor modulates basal and stress-induced excitatory amino acid release in the locus ceruleus of conscious rats. Neurosci Lett. 1996;204:45–48.CrossRefGoogle ScholarPubMed
16. McEwen, BS, Albeck, D, Cameron, H, et al. Stress and brain: a paradoxical role for adrenal steroids. In: Litwack, GD, ed. Vitamins and Hormones. San Diego, CA: Academic Press; 1995:371–402.Google Scholar
17. Moghaddam, B, Bolinao, ML, Stein-Behrens, B, et al. Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Res. 1994;655:251–254.Google Scholar
18. Gould, E, Tanapat, P. Stress and hippocampal neurogenesis. Biol Psychiatry. 1999;46:1472–1479.CrossRefGoogle ScholarPubMed
19. Cameron, HA, McEwen, BS, Gould, E. Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci. 1995;15:4687–4692.CrossRefGoogle ScholarPubMed
20. Jacobs, BL, van Praag, H, Gage, FH. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry. 2000;5:262–269.CrossRefGoogle ScholarPubMed
21. Kocsis, K, Kiss, J, Gores, T, et al. Metabotropic glutamate receptor in vasopressin, CRF and VIP hypothalamic neurons. Neuroreport. 1998;9:4029–4033.CrossRefGoogle Scholar
22. Mathew, SJ, Smith, ELP, Trost, RC, et al. Effects of chronic treatment with the novel metabotropic glutamate receptor agonist LY354740 in nonhuman primates: evidence for uncoupling of the HPA axis and noradrenergic system [abstract]. Young Investigators Abstract presented at American Psychiatric Association annual meeting; May 5-10, 2001; New Orleans, La.Google Scholar
23. Joanny, P, Steinberg, J, Oliver, C, et al. Glutamate and N-methyl-D-aspartate stimulate rat hypothalamic corticotropin-releasing factor secretion in vitro. J Neuroendocrinol. 1997;9:93–97.CrossRefGoogle ScholarPubMed
24. Tokarev, D, Jezova, D. Effect of central administration of the non-NMDA receptor antagonist DNQX on ACTH and corticosterone release before and during immobilization stress. Methods Find Exp Clin Pharmacol. 1997;19:323–328.Google ScholarPubMed
25. Zelena, D, Makara, GB, Jezova, D. Simultaneous blockade of two glutamate receptor subtypes (NMDA and AMPA) results in stressor-specific inhibition of prolactin and corticotropin release. Neuroendocrinology. 1999;69:316–323.CrossRefGoogle ScholarPubMed
26. Calabrese, JR, Bowden, CL, Sachs, GS, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999;60:79–88.CrossRefGoogle ScholarPubMed
27. Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351–354.CrossRefGoogle ScholarPubMed
28. Nowak, G, Ordway, GA, Paul, IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res. 1995;675:157–164.Google Scholar
29. Levine, J, Panchalingam, K, Rapoport, A, et al. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000;47:586–593.CrossRefGoogle ScholarPubMed
30. Auer, DP, Putz, B, Kraft, E, et al. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000;47:305–313.CrossRefGoogle Scholar
31. Rosenberg, DR, MacMaster, FP, Keshavan, MS, et al. Decrease in caudate glutamatergic concentrations in pediatric obsessive compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psych. 2000;39:1096–1103.CrossRefGoogle Scholar
32. Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54:597–606.CrossRefGoogle Scholar
33. Nibuya, M, Morinobu, S, Duman, RS. Regulation of BDNF and trkB mRNA following chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995;15:7539–7547.CrossRefGoogle Scholar
34. Altar, CA. Neurotrophins and depression. Trends Pharmacol Sci. 1999;20:59–61.CrossRefGoogle ScholarPubMed
35. Brandoli, C, Sanna, A, De Bernardi, MA, et al. Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci. 1998;18:7953–7961.CrossRefGoogle ScholarPubMed
36. Hayashi, T, Umemori, H, Mishina, M. The AMPA receptor interactions with and signals through the protein tyrosine kinase Lyn. Nature. 1999;397:72–76.Google Scholar
37. Caldji, C, Francis, D, Sharma, S, et al. The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and nov elty-induced fearfulness in the rat. Neuropsychopharmacology. 2000;22:219–229.CrossRefGoogle Scholar
38. Tanaka, K, Watase, K, Mabe, T, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 1997;276:1699–1702.CrossRefGoogle Scholar