Social isolation-induced increase in α4 and δ subunit gene expression is associated with a greater efficacy of ethanol on steroidogenesis and GABAA receptor function
J Neurochem. 2006-07-01; 98(1): 122-133
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1. J Neurochem. 2006 Jul;98(1):122-33.
Social isolation-induced increase in alpha and delta subunit gene expression is
associated with a greater efficacy of ethanol on steroidogenesis and GABA
Serra M(1), Mostallino MC, Talani G, Pisu MG, Carta M, Mura ML, Floris I,
Maciocco E, Sanna E, Biggio G.
(1)Department of Experimental Biology, University of Cagliari, Cagliari, Italy.
Previously we have demonstrated that social isolation of rats reduces both the
cerebrocortical and plasma concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one
(3alpha,5alpha-TH PROG), and potentiates the positive effects of acute ethanol
administration on the concentrations of this neurosteroid. We now show that the
ethanol-induced increase in 3alpha,5alpha-TH PROG is more pronounced in the brain
than in the plasma of isolated rats. The ability of ethanol to inhibit
isoniazid-induced convulsions is greater in isolated rats than in group-housed
animals and this effect is prevented by treatment with finasteride. Social
isolation modified the effects of ethanol on the amounts of steroidogenic
regulatory protein mRNA and protein in the brain. Moreover, ethanol increased the
amplitude of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents
recorded from CA1 pyramidal neurones with greater potency in hippocampal slices
prepared from socially isolated rats than in those from group-housed rats, an
effect inhibited by finasteride. The amounts of the alpha(4) and delta subunits
of the GABA(A) receptor in the hippocampus were increased in isolated rats as
were GABA(A) receptor-mediated tonic inhibitory currents in granule cells of the
dentate gyrus. These results suggest that social isolation results in changes in
GABA(A) receptor expression in the brain, and in an enhancement of the
stimulatory effect of ethanol on brain steroidogenesis, GABA(A) receptor function
and associated behaviour.
PMID: 16805802 [Indexed for MEDLINE]