| Abstrakt: |
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), anα2-adrenoceptor antagonist, significantly decreased the pentobarbital-induced sleeping time in group-housed but not in socially isolated mice while α-helical CRF9–41 (αhCRF; 3.3–6.5 nmol i.c.v.), a CRF antagonist, and clonidine (12.5–100 μg/kg i.p. and 7.5–15 nmol i.c.v.), anα2-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. αhCRF (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 β-adrenoceptor antagonist, and prazosin (5–10 nmol i.c.v. and 250–500 μg/kg i.p.), anα1-adrenergic antagonist, significantly and dose-dependently recovered the hypnotic activity of pentobarbital in socially isolated mice to the level in group-housed mice. Methoxamine (8–200 nmol i.c.v.), anα1-adrenergic antagonist, as well as CRF decreased the hypnotic activity of pentobarbital in group-housed mice in a dose-dependent manner and the effect of methoxamine was significantly blocked by αhCRF (6.5 nmol i.c.v.) On the other hand, pretreatment with DSP-4 (50 mg/kg i.p.; 3 days before testing), a selective noradrenaline neurotoxin, had no effect on the hypnotic activity of pentobarbital in group-housed or socially isolated mice whereas pretreatment with 6-OHDA and nomifensin (50 μg i.c.v. and 5 mg/kg i.p., respectively, 7 days before testing) significantly prevented the social isolation-induced decrease in the hypnotic activity of pentobarbital without affecting the activity observed in group-housed mice. Both DSP-4 and 6-OHDA treatment decreased noradrenaline (NA) contents in the cerebral cortex by ∼ 80% but the depletion of the hypothalamic NA after 6-OHDA + nomifensin (40–52%) was more marked than that after DSP-4 (22–24%,P < 0.01). These results suggest that the social isolation-induced decrease in the hypnotic activity of pentobarbital involves the hyperactivity of CRF system through NA stimulation ofα1-and/or β-adrenoceptor in mice. |
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