Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain

The effects of social isolation on behavior, neuroactive steroid concentrat ions, and GABA(A) receptor function were investigated in rats. Animals isol ated for 30 days immediately after weaning exhibited an anxiety-like behavi oral profile in the elevated plus-maze and Vogel conflict tests. This behav ior was associated with marked decreases in the cerebrocortical, hippocampa l, and plasma concentrations of pregnenolone, progesterone, allopregnanolon e, and allotetrahydrodeoxycorticosterone compared with those apparent for g roup-housed rats; in contrast, the plasma concentration of corticosterone w as increased in the isolated animals. Acute footshock stress induced greate r percentage increases in the cortical concentrations of neuroactive steroi ds in isolated rats than in group-housed rats. Social isolation also reduce d brain GABA(A) receptor function, as evaluated by measuring both GABA-evok ed CI- currents in Xenopus oocytes expressing the rat receptors and tert-[S -35]butylbicyclophosphorothionate ([S-35]TBPS) binding to rat brain membran es. Whereas the amplitude of GABA-induced CI- currents did not differ signi ficantly between group-housed and isolated animals, the potentiation of the se currents by diazepam was reduced at cortical or hippocampal GABA(A) rece ptors from isolated rats compared with that apparent at receptors from grou p-housed animals. Moreover, the inhibitory effect of ethyl-beta-carboline-3 -carboxylate, a negative allosteric modulator of GABA(A) receptors, on thes e currents was greater at cortical GABA(A) receptors from socially isolated animals than at those from group-housed rats. Finally, social isolation in creased the extent of [S-35]TBPS binding to both cortical and hippocampal m embranes. The results further suggest a psychological role for neurosteroid s and GABA(A) receptors in the modulation of emotional behavior and mood.