The effect of cyanamide and 4-methylpyrazole on the ethanol-induced locomotor activity in mice

To assess the role of cyanamide and 4-methylpyrazole (4-MP) in mediating ethanol-induced locomotor activity in mice, they were pretreated with cyanamide (12.5, 25, or 50 g/kg) prior to one ethanol injection (2.4 g/kg) and showed significantly depressed locomotor activity compared with control groups. Cyanamide (25 mg/kg) also cancelled out the biphasic action of ethanol (0, 0.8, 1.6, 2.4, 3.2, or 4 g/kg) on locomotor activity. The action of cyanamide and 4-MP in combined administration was also tested. Our data show that pretreatment with 4-MP alone does not change the spontaneous or ethanol-induced locomotor activity. Conversely, when mice were pretreated with cyanamide and 4-MP, the depressive effect of cyanamide on the locomotor activity induced by ethanol disappeared, and the locomotor activity rose to levels similar to those of the control group, recovering the biphasic ethanol effect. These effects cannot be attributed to peripheral elevated blood acetaldehyde levels, as pretreatment with 4-MP prevents accumulation of acetaldehyde. These data might suggest some influence of brain catalase and aldehyde dehydrogenase (ALDH) on the effects of ethanol.