title: Effects of cyanamide and acetaldehyde accumulation on the locomotor stimulant and sedative effects of ethanol in mice.
abstract: Ethanol administration induces both locomotor stimulant and sedative effects depending upon blood ethanol concentrations. Recent studies in rats and mice suggest that acetaldehyde, the first product of ethanol metabolism, might be involved in the expression of both the stimulant and the sedative effects of ethanol. A number of studies have used the drug cyanamide in an attempt to clarify the role of acetaldehyde in the behavioral effects of ethanol. The results of such studies are, however, difficult to interpret because cyanamide is an inhibitor of the enzymes catalase and aldehyde dehydrogenase, two enzymes with opposite effects on brain acetaldehyde concentrations. This study was aimed at clarifying the effects of cyanamide on ethanol-induced locomotor stimulant and sedative effects in Swiss mice. The locomotor stimulant effects of ethanol were measured in standard activity boxes, whereas the sedative effects of ethanol were quantified using the loss of righting reflex procedure. Cyanamide prevented the locomotor stimulant effects of 2 g/kg ethanol, although this was mainly due to a potentiation of the inhibitory effects of ethanol as evidenced by a prolongation of ethanol-induced loss of righting reflex. Additionally, 4-methylpyrazole, an inhibitor of the enzyme alcohol dehydrogenase, prevented these effects of cyanamide. It is concluded that in vivo the effects of cyanamide are predominantly due to the inhibition of the enzyme aldehyde dehydrogenase, rather than to its effects on catalase.
authors.affiliation: Center of Cognitive and Behavioral Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tambour
authors.forename: Catherine
authors.initials: C
authors.lastname: Closon
authors.forename: Ezio
authors.initials: E
authors.lastname: Tirelli
authors.forename: Etienne
authors.initials: E
authors.lastname: Quertemont
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D011720:Pyrazoles; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde