Social Isolation-Induced Decreases in Both the Abundance of Neuroactive Steroids and GABA sub(A) Receptor Function in Rat Brain

• Published in: Journal of neurochemistry 2000-08, Vol.75 (2), p.732-740
• Main Authors: Serra, M, Pisu, M G, Littera, M, Papi, G, Sanna, E, Tuveri, F, Usala, L, Purdy, R H, Biggio, G
• Format: Article
• Language: English
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.2000.0750732.x

The effects of social isolation on behavior, neuroactive steroid concentrations, and GABA sub(A) receptor function were investigated in rats. Animals isolated for 30 days immediately after weaning exhibited an anxiety-like behavioral profile in the elevated plus-maze and Vogel conflict tests. This behavior was associated with marked decreases in the cerebrocortical, hippocampal, and plasma concentrations of pregnenolone, progesterone, allopregnanolone, and allotetrahydrodeoxycorticosterone compared with those apparent for group-housed rats; in contrast, the plasma concentration of corticosterone was increased in the isolated animals. Acute footshock stress induced greater percentage increases in the cortical concentrations of neuroactive steroids in isolated rats than in group-housed rats. Social isolation also reduced brain GABA sub(A) receptor function, as evaluated by measuring both GABA-evoked Cl super(-) currents in Xenopus oocytes expressing the rat receptors and tert-[ super(35)S] butylbicyclophosphorothionate ([ super(35)S]TBPS) binding to rat brain membranes. Whereas the amplitude of GABA-induced Cl super(-) currents did not differ significantly between group-housed and isolated animals, the potentiation of these currents by diazepam was reduced at cortical or hippocampal GABA sub(A) receptors from isolated rats compared with that apparent at receptors from group-housed animals. Moreover, the inhibitory effect of ethyl-ss-carboline-3-carboxylate, a negative allosteric modulator of GABA sub(A) receptors, on these currents was greater at cortical GABA sub(A) receptors from socially isolated animals than at those from group-housed rats. Finally, social isolation increased the extent of [ super(35)S]TBPS binding to both cortical and hippocampal membranes. The results further suggest a psychological role for neurosteroids and GABA sub(A) receptors in the modulation of emotional behavior and mood.