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
Article first published online: 4 MAY 2006
Journal of Neurochemistry
Volume 98, Issue 1, pages 122–133, July 2006
How to Cite
Serra, M., Mostallino, M. C., Talani, G., Pisu, M. G., Carta, M., Mura, M. L., Floris, I., Maciocco, E., Sanna, E. and Biggio, G. (2006), 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. Journal of Neurochemistry, 98: 122–133. doi: 10.1111/j.1471-4159.2006.03850.x
- Issue published online: 30 MAY 2006
- Article first published online: 4 MAY 2006
- Received November 30, 2005; revised manuscript received February 6, 2006; accepted February 8, 2006.
- γ-aminobutyric acidA receptor;
- miniature inhibitory postsynaptic current;
- social isolation
Previously we have demonstrated that social isolation of rats reduces both the cerebrocortical and plasma concentrations of 3α-hydroxy-5α-pregnan-20-one (3α,5α-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 3α,5α-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 GABAA 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 α4 and δ subunits of the GABAA receptor in the hippocampus were increased in isolated rats as were GABAA receptor-mediated tonic inhibitory currents in granule cells of the dentate gyrus. These results suggest that social isolation results in changes in GABAA receptor expression in the brain, and in an enhancement of the stimulatory effect of ethanol on brain steroidogenesis, GABAA receptor function and associated behaviour.