Hyperactivity of central noradrenergic and CRF systems is involved in social isolation-induced decrease in pentobarbital sleep.

The modulatory effects of the central noradrenergic and CRF systems on the pentobarbital-induced hypnotic activity were investigated in socially isolated mice. Pentobarbital-induced sleeping time decreased depending on the duration of isolation period and reached the minimum at 4 weeks after the isolation. The intermale aggressive behavior tested in isolated mice increased along with the decrease of hypnotic activity of pentobarbital. I.c.v. injection of CRF (corticotropin-releasing factor; 0.6-2.1 nmol) and i.p. injection of yohimbine (0.5-1 mg/kg), an alpha 2-adrenoceptor antagonist, significantly decreased the pentobarbital-induced sleeping time in group-housed but not in socially isolated mice while alpha-helical CRF9-41 (alpha hCRF; 3.3-6.5 nmol i.c.v.), a CRF antagonist, and clonidine (12.5-100 micrograms/kg i.p. and 7.5-15 nmol i.c.v.), an alpha 2-adrenoceptor agonist, recovered the hypnotic activity of pentobarbital decreased by social isolation to the level in group-housed mice without changing the activity observed in group-housed animals. alpha hCRF (6.5 nmol i.c.v.) significantly abolished the yohimbine (1 mg/kg i.p.)-induced decrease in the hypnotic activity of pentobarbital in group-housed mice. Propranolol (50-100 nmol i.c.v. and 5-10 mg/kg i.p.), a beta-adrenoceptor antagonist, and prazosin (5-10 nmol i.c.v. and 250-500 micrograms/kg i.p.), an alpha 1-adrenergic antagonist, significantly and dose-dependently recovered the hypnotic activity of pentobarbital in socially isolated mice to the level in group-housed mice.(ABSTRACT TRUNCATED AT 250 WORDS)