Impact of early-life stress, on group III mGlu receptor levels in the rat hippocampus: effects of ketamine, electroconvulsive shock therapy and fluoxetine treatment.

Richard M O' Connor, Matteo M Pusceddu, Timothy G Dinan, John F Cryan

School of Pharmacy, University College Cork, Ireland.

Neuropharmacology 2013 Mar

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The glutamatergic system is increasingly being viewed as a promising target for the development of novel treatments for depression. The group III metabotropic glutamate (mGlu) receptors (mGlu(4, 7) and (8) receptors) in particular are beginning to show promise in this respect. It remains unclear how antidepressant medications modulate mGlu receptors. In this study we investigated the effects of three antidepressant treatments (fluoxetine, ketamine and electroconvulsive shock therapy (ECT)). Ketamine is an NMDA receptor antagonist which possess a rapid antidepressant therapeutic profile and moreover is effective in cases of treatment-resistant depression. Furthermore, ECT is also a therapeutic strategy possessing increased efficacy compared to conventional monoamine based therapies. The effect these two highly efficacious treatments have on hippocampal group III mGlu receptors remains completely unexplored. To redress this deficit we investigated the effects these treatments and the prototypical selective serotonin reuptake inhibitor (SSRI) fluoxetine would have on hippocampal group III mGlu receptor mRNA levels in naïve Sprague-Dawley rats and rats which had undergone early-life stress in the form of the maternal separation (MS) procedure. We found MS significantly reduced mGlu(4) receptor expression and fluoxetine reversed this MS induced change. ECT and ketamine treatment significantly reduced mGlu(4) receptor expression in non-separated (NS) animals while having no effect in MS animals. Fluoxetine and ECT significantly increased mGlu(7) receptor expression in NS animals. This work demonstrates changes to mGlu(4) receptor expression may be a lasting molecular change which occurs due to early-life stress. Taken together our data shows there are selective changes to group III mGlu receptors under basal and early-life stress conditions. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Richard M O' Connor, Matteo M Pusceddu, Timothy G Dinan, John F Cryan. Impact of early-life stress, on group III mGlu receptor levels in the rat hippocampus: effects of ketamine, electroconvulsive shock therapy and fluoxetine treatment. Neuropharmacology. 2013 Mar;66:236-41