Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression

Anteneh Feyissa, William L. Woolverton, Jose J. Miguel-Hidalgo, Zhixia Wang, Patrick B. Kyle, Gregor Hasler, Craig A. Stockmeier, Abiye H. Iyo, Beata Karolewicz

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Clinical, postmortem and preclinical research strongly implicates dysregulation of glutamatergic neurotransmission in major depressive disorder (MDD). Recently, metabotropic glutamate receptors (mGluRs) have been proposed as attractive targets for the discovery of novel therapeutic approaches against depression. The aim of this study was to examine mGluR2/3 protein levels in the prefrontal cortex (PFC) from depressed subjects. In addition, to test whether antidepressants influence mGluR2/3 expression we also studied levels of mGluR2/3 in fluoxetine-treated monkeys. Postmortem human prefrontal samples containing Brodmann's area 10 (BA10) were obtained from 11 depressed and 11 psychiatrically healthy controls. Male rhesus monkeys were treated chronically with fluoxetine (dose escalated to 3. mg/kg, p.o.; n=7) or placebo (n=6) for 39. weeks. The mGluR2/3 immunoreactivity was investigated using Western blot method. There was a robust (+. 67%) increase in the expression of the mGlu2/3 protein in the PFC of depressed subjects relative to healthy controls. The expression of mGlu2/3 was unchanged in the PFC of monkeys treated with fluoxetine. Our findings provide the first evidence that mGluR2/3 is elevated in the PFC in MDD. This observation is consistent with reports showing that mGluR2/3 antagonists exhibit antidepressant-like activity in animal models and demonstrates that these receptors are promising targets for the discovery of novel antidepressants.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume34
Issue number2
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Prefrontal Cortex
Depression
Fluoxetine
Antidepressive Agents
Major Depressive Disorder
Haplorhini
Metabotropic Glutamate Receptors
Macaca mulatta
Synaptic Transmission
metabotropic glutamate receptor 3
metabotropic glutamate receptor 2
Proteins
Animal Models
Western Blotting
Placebos
Research

Keywords

  • Fluoxetine
  • Major depression
  • Metabotropic glutamate receptor
  • Postmortem
  • Prefrontal cortex
  • Rhesus monkey

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this

Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. / Feyissa, Anteneh; Woolverton, William L.; Miguel-Hidalgo, Jose J.; Wang, Zhixia; Kyle, Patrick B.; Hasler, Gregor; Stockmeier, Craig A.; Iyo, Abiye H.; Karolewicz, Beata.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 34, No. 2, 01.01.2010, p. 279-283.

Research output: Contribution to journalArticle

Feyissa, A, Woolverton, WL, Miguel-Hidalgo, JJ, Wang, Z, Kyle, PB, Hasler, G, Stockmeier, CA, Iyo, AH & Karolewicz, B 2010, 'Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 34, no. 2, pp. 279-283. https://doi.org/10.1016/j.pnpbp.2009.11.018
Feyissa, Anteneh ; Woolverton, William L. ; Miguel-Hidalgo, Jose J. ; Wang, Zhixia ; Kyle, Patrick B. ; Hasler, Gregor ; Stockmeier, Craig A. ; Iyo, Abiye H. ; Karolewicz, Beata. / Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2010 ; Vol. 34, No. 2. pp. 279-283.
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