Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation

Proceedings of the National Academy of Sciences of the United States of America
G PinnaA Guidotti

Abstract

In cortex and hippocampus, protracted (>4 weeks) social isolation of adult male mice alters the subunit expression of GABA type A receptors (GABA(A)-Rs) as follows: (i) the mRNAs encoding GABA(A)-R alpha1, alpha2, and gamma2 subunits are decreased by approximately 50%, whereas those encoding alpha4 and alpha5 subunits are increased by approximately 100%; (ii) similarly, the synaptic membrane expression of the alpha1 subunit protein is down-regulated, and that of the alpha5 subunit protein is up-regulated; and (iii) the binding of [(3)H]flumazenil to hippocampal synaptic membranes is decreased. Behaviorally, socially isolated (SI) mice are resistant to the sedative effects of the positive allosteric GABA(A)-R modulators diazepam (DZP) and zolpidem. This resistance seems to be attributable to the decrease of alpha1-containing GABA(A)-Rs. Paradoxically, DZP, which, unlike zolpidem, acts at alpha5-containing GABA(A)-Rs, increases the locomotor activity of SI mice. Imidazenil, which fails to modulate alpha1-, alpha4-, and alpha6-containing GABA(A)-Rs but is a selective positive allosteric modulator of alpha5-containing GABA(A)-Rs, also increases locomotor activity in SI mice. Importantly, SI mice responded to muscimol, 4,5,6,7-tetra...Continue Reading

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Citations

May 12, 2012·Neuroendocrinology·Joseph G OberlanderLeslie P Henderson
Apr 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fabio PibiriGraziano Pinna
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Roberto C Agís-BalboaAlessandro Guidotti
Oct 19, 2010·Neuropharmacology·S J Enna
Nov 3, 2011·Stress : the International Journal on the Biology of Stress·Shlomit Jacobson-Pick, Gal Richter-Levin
Jul 8, 2008·Journal of Pharmacological Sciences·Hidenori SagaraYutaka Gomita
Jul 13, 2016·Behavioural Brain Research·Irene Joy I Dela PeñaJae Hoon Cheong
Aug 26, 2016·Journal of Pharmacological Sciences·Nobuaki EgashiraKatsunori Iwasaki
Jun 28, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Alessandro Guidotti, Dennis R Grayson
Jan 26, 2010·Immunopharmacology and Immunotoxicology·R LazzariniJ Palermo-Neto
Aug 8, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Yi-Ting HsuYijuang Chern
Jun 28, 2019·Frontiers in Behavioral Neuroscience·Graziano Pinna
May 14, 2008·Neurochemical Research·Graziano PinnaErminio Costa
Jun 2, 2020·Frontiers in Endocrinology·Graziano Pinna
Aug 23, 2018·Frontiers in Neuroscience·Graziano Pinna
Feb 4, 2021·PloS One·D Gregory SullensMelanie J Sekeres
Feb 6, 2021·The Science of the Total Environment·Xiangsheng HongJinmiao Zha

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