title: Social isolation-induced increase in alpha and delta subunit gene expression is associated with a greater efficacy of ethanol on steroidogenesis and GABA receptor function.
abstract: 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.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Cagliari, Italy. mserra@unica.it
authors.forename: Mariangela
authors.initials: M
authors.lastname: Serra
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mostallino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Pisu
authors.forename: Mario
authors.initials: M
authors.lastname: Carta
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mura
authors.forename: Ivan
authors.initials: I
authors.lastname: Floris
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Maciocco
authors.forename: Enrico
authors.initials: E
authors.lastname: Sanna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011280:Pregnanolone / Q000097:blood / Q000134:cerebrospinal fluid; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012934:Social Isolation
chemical_list: D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D012333:RNA, Messenger; D018079:Receptors, GABA; D000431:Ethanol; D018120:Finasteride; D011280:Pregnanolone; D001640:Bicuculline