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 mM) 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.

DEFECTIVE GROUP-II METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS OF SPONTANEOUSLY DEPRESSED RATS / Matrisciano, Francesco; Caruso, Alessandra Sebastiana Maria; Orlando, Rosamaria; Marchiafava, M; Bruno, Valeria Maria Gloria; Battaglia, Giuseppe; Gruber, Shm; Melchiorri, Daniela; Tatarelli, Roberto; Girardi, Paolo; Mathè, Aa; Nicoletti, Ferdinando. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 55:(2008), pp. 525-531. [10.1016/j.neuropharm.2008.05.014]

DEFECTIVE GROUP-II METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS OF SPONTANEOUSLY DEPRESSED RATS

MATRISCIANO, FRANCESCO;CARUSO, Alessandra Sebastiana Maria;ORLANDO, Rosamaria;BRUNO, Valeria Maria Gloria;BATTAGLIA, Giuseppe;MELCHIORRI, Daniela;TATARELLI, Roberto;GIRARDI, Paolo;NICOLETTI, Ferdinando
2008

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 mM) 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.
2008
01 Pubblicazione su rivista::01a Articolo in rivista
DEFECTIVE GROUP-II METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS OF SPONTANEOUSLY DEPRESSED RATS / Matrisciano, Francesco; Caruso, Alessandra Sebastiana Maria; Orlando, Rosamaria; Marchiafava, M; Bruno, Valeria Maria Gloria; Battaglia, Giuseppe; Gruber, Shm; Melchiorri, Daniela; Tatarelli, Roberto; Girardi, Paolo; Mathè, Aa; Nicoletti, Ferdinando. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 55:(2008), pp. 525-531. [10.1016/j.neuropharm.2008.05.014]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/366171
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 51
  • ???jsp.display-item.citation.isi??? 42
social impact