The ability of divalent cations to enhance ethanol-induced sleeping time

This investigation was carried out to determine if prolongation of ethanol-induced sleep by divalent cations is mediated by calmodulin (CaM) and biogenic amine. The effects of CaM antagonist, W-7:[N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide], serotonin (5-HT) synthesizing enzyme inhibitor, p-chlorophenylalanine (PCPA), and catecholamine synthesizing enzyme inhibitor, alpha-methyltyrosine (alpha MPT) on ethanol-induced sleeping time enhanced by divalent cations were studied in ddY male mice. The ethanol-induced sleeping time was increased by 70, 200, 180, 70, and 45% by intraventricular (IVT) injection of CaCl2 (10 mumol/kg), MnCl2 (15 mumol/kg), ZnCl2 (2.5 mumol/kg), CdCl2 (1 mumol/kg), and HgCl2 (1 mumol/kg), respectively, compared to the saline group. On the other hand, when mice were treated IVT with W-7 and their divalent cation, the sleeping time induced by ethanol was decreased compared to that of the cation without W-7 treated mice. Also, when mice were injected simultaneously with either PCPA or alpha MPT and CaCl2, ZnCl2, CdCl2, or HgCl2, the ethanol-induced sleeping time was less compared to those given saline together with their cation, respectively. These results would suggest a probable mechanism in which Ca++, Zn++, Cd++, and Hg++ prolong ethanol-induced sleeping time by activating biogenic amine synthesizing enzymes through cerebral CaM and CaM-dependent protein kinase.