Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats

Marco Pignatelli, Barbara Vollmayr, Sophie Helene Richter, Silvia Middei, Francesco Matrisciano, Gemma Molinaro, Carla Nasca, Giuseppe Battaglia, Martine Ammassari-Teule, Marco Feligioni, Robert Nisticò, Ferdinando Nicoletti, Peter Gass

Research output: Contribution to journalArticle

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Abstract

Alterations of the glutamatergic system have been implicated in the pathophysiology and treatment of major depression. In order to investigate the expression and function of mGlu5 receptors in an animal model for treatment-resistant depression we used rats bred for congenital learned helplessness (cLH) and the control strain, bred for resistance against inescapable stress, congenitally. not learned helpless rats (cNLH). Western blot analysis showed an increased expression of mGlu5 (but not mGlu1a) receptors in the hippocampus of cLH rats, as compared with control cNLH rats. We also examined mGlu1/5 receptor signaling by in vivo measurement of DHPG-stimulated polyphosphoinositides hydrolysis. Stimulation of 3H- inositolmonophosphate formation induced by i.c.v. injection of DHPG was enhanced by about 50% in the hippocampus of cLH rats. Correspondingly, DHPG-induced long-term depression (LTD) at Schaffer collateral/CA1 pyramidal cell synapses was amplified in hippocampal slices of cLH rats, whereas LTD induced by low frequency stimulation of the Schaffer collaterals did not change. Moreover, these effects were associated with decreased basal dendritic spine density of CA1 pyramidal cell in cLH rats. These data raise the attractive possibility that changes in the expression and function of mGlu5 receptors in the hippocampus might underlie the changes in synaptic plasticity associated with the depressive-like phenotype of cLH rats. However, chronic treatment of cLH rats with MPEP did not reverse learned helplessness, indicating that the enhanced mGlu5 receptor function is not the only player in the behavioral phenotype of this genetic model of depression. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

Original languageEnglish (US)
Pages (from-to)339-347
Number of pages9
JournalNeuropharmacology
Volume66
DOIs
StatePublished - Mar 1 2013

Fingerprint

Learned Helplessness
Synapses
Hippocampus
Depression
Pyramidal Cells
Treatment-Resistant Depressive Disorder
Behavioral Genetics
Phenotype
Phosphatidylinositol Phosphates
Dendritic Spines
Metabotropic Glutamate Receptors
Neuronal Plasticity
Genetic Models
Hydrolysis
Animal Models
Western Blotting
Injections

Keywords

  • Depression-like behavior
  • Hippocampus
  • Learned helplessness
  • LTD
  • mGlu5 receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats. / Pignatelli, Marco; Vollmayr, Barbara; Richter, Sophie Helene; Middei, Silvia; Matrisciano, Francesco; Molinaro, Gemma; Nasca, Carla; Battaglia, Giuseppe; Ammassari-Teule, Martine; Feligioni, Marco; Nisticò, Robert; Nicoletti, Ferdinando; Gass, Peter.

In: Neuropharmacology, Vol. 66, 01.03.2013, p. 339-347.

Research output: Contribution to journalArticle

Pignatelli, M, Vollmayr, B, Richter, SH, Middei, S, Matrisciano, F, Molinaro, G, Nasca, C, Battaglia, G, Ammassari-Teule, M, Feligioni, M, Nisticò, R, Nicoletti, F & Gass, P 2013, 'Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats', Neuropharmacology, vol. 66, pp. 339-347. https://doi.org/10.1016/j.neuropharm.2012.05.046
Pignatelli, Marco ; Vollmayr, Barbara ; Richter, Sophie Helene ; Middei, Silvia ; Matrisciano, Francesco ; Molinaro, Gemma ; Nasca, Carla ; Battaglia, Giuseppe ; Ammassari-Teule, Martine ; Feligioni, Marco ; Nisticò, Robert ; Nicoletti, Ferdinando ; Gass, Peter. / Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats. In: Neuropharmacology. 2013 ; Vol. 66. pp. 339-347.
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AU - Vollmayr, Barbara

AU - Richter, Sophie Helene

AU - Middei, Silvia

AU - Matrisciano, Francesco

AU - Molinaro, Gemma

AU - Nasca, Carla

AU - Battaglia, Giuseppe

AU - Ammassari-Teule, Martine

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