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

Abstract

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-l-naphthalenesulfonamide], serotonin (5-HT) synthesizing enzyme inhibitor, p-chlorophenylalanine (PCPA), and catecholamine synthesizing enzyme inhibitor, α-methyltyrosine (αMPT) 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 CaCl 2 (10 μmol/kg), MnCl 2 (15 μmol/kg), ZnCl 2 (2.5 μmol/kg), CdCl 2 (1 μmol/kg), and HgCl 2 (1 μmol/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 αMPT and CaCl 2, ZnCl 2, CdCl 2, or HgCl 2, 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.