title: Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression.
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 3mg/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.
authors: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Anteneh M
authors: AM
authors: Feyissa
authors: William L
authors: WL
authors: Woolverton
authors: Jose J
authors: JJ
authors: Miguel-Hidalgo
authors: Zhixia
authors: Z
authors: Wang
authors: Patrick B
authors: PB
authors: Kyle
authors: Gregor
authors: G
authors: Hasler
authors: Craig A
authors: CA
authors: Stockmeier
authors: Abiye H
authors: AH
authors: Iyo
authors: Beata
authors: B
authors: Karolewicz
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000473:pathology*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D005473:Fluoxetine