Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus

Isabella Panaccione; Luisa Iacovelli; Luigi di Nuzzo; Francesca Nardecchia; Gianluca Mauro; Delfina Janiri; Antonio De Blasi; Gabriele Sani; Ferdinando Nicoletti; Rosamaria Orlando

doi:10.1016/j.phrs.2016.11.029

Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus

Pharmacol Res. 2017 Mar:117:46-53. doi: 10.1016/j.phrs.2016.11.029. Epub 2016 Nov 23.

Affiliations

¹ Unit of Psychiatry, Department of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.), Faculty of Medicine and Psychology, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.
² Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
³ Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy.
⁴ Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Via dei Sabelli 108, 00185 Rome, Italy.
⁵ Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy.
⁶ Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.
⁷ Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; IRCCS Neuromed, Località Camerelle, 86077 Pozzilli (IS), Italy.
⁸ Department of Physiology and Pharmacology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy. Electronic address: rosamariaorlando@hotmail.com.

PMID: 27890550
DOI: 10.1016/j.phrs.2016.11.029

Abstract

Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the prefrontal cortex or corpus striatum, as compared to both groups of control rats. No changes in the expression of mGlu3 receptor mRNA levels or mGlu1α and mGlu5 receptor protein levels were found with exception of an increase in mGlu1α receptor levels in the striatum of SD rats. Moving from these findings we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA (30mg/kg, i.p.). SD rats were also treated with sodium valproate (300mg/kg, i.p.) as an active comparator. Both BINA and sodium valproate were effective in reversing the manic-like phenotype evaluated in an open field arena in SD rats. BINA treatment had no effect on motor activity in control rats, suggesting that our findings were not biased by a non-specific motor-lowering activity of BINA. These findings suggest that changes in the expression of mGlu2 receptors may be associated with the enhanced motor activity observed with mania.

Keywords: BINA; Motor activity; Paradoxical sleep deprivation; mGlu2 receptor.

MeSH terms

Animals
Hippocampus / metabolism*
Male
Motor Activity / physiology
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate / metabolism*
Sleep / physiology*
Sleep Deprivation / metabolism*

Substances

RNA, Messenger
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 2