Central corticotropin-releasing factor and benzodiazepine receptor systems are involved in the social isolation stress-induced decrease in ethanol sleep in mice

Social isolation stress has been demonstrated to decrease the hypnotic activity of ethanol in rodents. In this study, the role of central corticotropin-releasing factor (CRF) and GABA(A)/benzodiazepine (BZD) receptor systems in the social isolation stress-induced decrease in the hypnotic activity of ethanol in mice was investigated by examining the effect of alpha-helical CRF(9-41) (alpha hCRF) and flumazenil, antagonists of CRF and BZD receptors, respectively, on ethanol-induced sleep in group-housed and socially isolated mice. We also tested whether social isolation stress affects the ability of ethanol to enhance the GABA-induced Cl-36(-) influx into a synaptoneurosomal preparation of mouse forebrain. Social isolation stress significantly decreased both the ethanol (4 g/kg i.p.)-induced and pentobarbital (50 mg/kg i.p.)-induced sleeping times, while this stress had no effect on chloral hydrate (325 mg/kg i.p.)-induced sleep. The i.c.v. injection of alpha hCRF (6.5 nmol) and flumazenil (33 nmol) antagonized the social isolation stress-induced decrease in the ethanol sleep without affecting ethanol sleep in group-housed animals. Social isolation stress significantly attenuated the ability of GABA to stimulate 36 but this stress had no effect on the ability of ethanol to enhance GABA-induced Cl-36(-) influx. These results suggest that the functional changes in central CRF and GABA(A)/BZD receptor systems are involved in the social isolation stress-induced decrease in the hypnotic activity of ethanol in mice. (C) 1997 Elsevier Science B.V.