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 36Cl- 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 36Cl- influx but this stress had no effect on the ability of ethanol to enhance GABA-induced 36Cl- 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.
Matsumoto
K
K
Department of Pharmacology, Toyama Medical and Pharmaceutical University, Sugitani, Japan. mkinzo@ms.toyama-mpu.ac.jp
Ojima
K
K
Watanabe
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006727:Hormone Antagonists / Q000494:pharmacology; D006799:Housing, Animal; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000502:physiology*; D012890:Sleep / Q000187:drug effects*; D012934:Social Isolation; D013315:Stress, Psychological / Q000503:physiopathology*; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002492:Central Nervous System Depressants; D002712:Chlorides; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D006727:Hormone Antagonists; D011963:Receptors, GABA-A; C069206:alpha helical corticotropin-releasing hormone; D000431:Ethanol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone