Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats

F. Matrisciano, A. Caruso, R. Orlando, M. Marchiafava, V. Bruno, G. Battaglia, S. H M Gruber, D. Melchiorri, R. Tatarelli, P. Girardi, A. A. Mathè, F. Nicoletti

Research output: Contribution to journalArticle

Abstract

Spontaneously depressed flinders sensitive line (FSL) rats showed a reduced expression of mGlu2/3 metabotropic glutamate receptors in the hippocampus, as compared to "non-depressed" flinders resistant line (FRL) rats. No changes in mGlu2/3 receptor protein levels were found in other brain regions, including the amygdala, hypothalamus, and cerebral cortex. Biochemical analysis of receptor signalling supported the reduction of mGlu2/3 receptors in the hippocampus of FSL rats. Accordingly, the selective mGlu2/3 receptor agonist, LY379268 (1 μM) reduced forskolin-stimulated cAMP formation by 56% and 32% in hippocampal slices from FRL and FSL rats, respectively. In addition, LY379268 enhanced 3,5-dihydroxyphenylglycine-stimulated inositol phospholipid hydrolysis from 65% to 215% in hippocampal slices from FRL rats, whereas it was inactive in slices from FRL rats. We also examined the behavioural response of FSL rats to systemic injection of LY379268 (0.5 mg/kg, i.p., once a day for 1-21 days) by measuring the immobility time in the forced swim test, which is known to be increased in these rats. LY379268 was administered alone or combined with the classical antidepressant, chlorimipramine (10 mg/kg, i.p.). LY379268 alone had no effect at any of the selected time-points, whereas chlorimipramine alone reduced the immobility time only after 21 days of treatment. In contrast, when combined with LY379268, chlorimipramine reduced the immobility time during the first 14 days of treatment. These data support the view that mGlu2/3 receptors might be involved in the pathophysiology of depressive disorders, and that pharmacological activation of these receptors may shorten the latency of antidepressant medication.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalNeuropharmacology
Volume55
Issue number4
DOIs
Publication statusPublished - Sep 2008

Keywords

  • Depression
  • FSL rats
  • Hippocampus
  • Metabotropic glutamate receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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  • Cite this

    Matrisciano, F., Caruso, A., Orlando, R., Marchiafava, M., Bruno, V., Battaglia, G., Gruber, S. H. M., Melchiorri, D., Tatarelli, R., Girardi, P., Mathè, A. A., & Nicoletti, F. (2008). Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats. Neuropharmacology, 55(4), 525-531. https://doi.org/10.1016/j.neuropharm.2008.05.014