RESTRAINT CHANGES PENTOBARBITAL-INDUCED SLEEPING TIME IN RATS - EVIDENCE THAT AROUSAL IS MODULATED BY BRAIN CORTICOTROPIN-RELEASING HORMONE AND OPIOID IN STRESS

The effect of restraint of different duration on sodium pentobarbital (PbNa)-induced sleeping time was examined in rats. 1 h-restraint significantly shortened PbNa (50 mg/kg b.wt., administered i.p. immediately after restraint)-induced sleeping time as reported previously, whereas 2 h-restraint significantly prolonged the sleeping time. Naloxone (1 mg/kg b.wt.) administered i.p. 15 min before the start of restraint further exaggerated the 1 h-restraint-caused shortening of PbNa-induced sleeping time, and it blocked the 2 h-restraint-caused prolongation of the sleeping time. SDZ202-250 (0.1 pmol and 0.5 pmol), a selective mu agonist, but not [D-Pen(2)-D-Pen(5)]enkephalin (0.1 pmol-1.0 nmol), a selective delta agonist, or U50488H (0.1 pmol-1.0 nmol), a selective kappa agonist, administered i.c.v. 15 min before the i.p. injection of PbNa significantly prolonged PbNa-induced sleeping time; its prolongation was blocked by naloxone. These results suggest that a mu receptor-binding opioid prolongs PbNa-induced sleeping time in stress. The 2 h-restraint-caused prolongation of PbNa-induced sleeping time was also blocked by alpha-helical CRH(9-41) (26 nmol), a corticotropin-releasing hormone (CRH) receptor antagonist, administered i.c.v. 15 min before the start of restraint. In conjunction with our previous findings that the i.c.v. administration of CRH shortens PbNa-induced sleeping time and the 1 h restraint-caused shortening of PbNa-induced sleeping time is blocked by the CRH receptor antagonist, the present results suggest that CRH may stimulate an opioid-specific sedative mechanism, thus causing the prolongation of PbNa-induced sleeping time in 2 h-restraint. It is concluded from these results that arousal is modulated by brain CRH and a mu receptor-binding opioid in stress; it is also concluded that the action of CRH is dominant in 1 h-restraint and that of opioid is dominant in longer restraint.