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

Stabilization of IGFBP-1 mRNA by ethanol in hepatoma cells involves the JNK pathway

“…Cyanamide inhibits catalase and aldehyde dehydrogenase activity; 4-methylpyrazole is an inhibitor of both alcohol dehydrogenase and CYP2E1 [29], diallyl sulfide (DAS) is a selective inhibitor of CYP2E1 [30]. None of these compounds decreased the ethanol effect on IGFBP-1 expression (Fig.…”

Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

“…Hence, provided that ethanol is not a substrate of brain ADH isoforms, the effect of the ADH competitive inhibitor, 4-methylpyrazole (4-MP), mostly used in behavioral studies is restricted to the peripheral metabolism of ethanol (Escarabajal and Aragon, 2002). In this paragraph we will focus our attention mostly on studies in which, to mimic the route commonly used by humans, ethanol and ACD were administered orally.…”

“…Notably, a consistent body of evidence, suggesting that to exert its motivational properties ethanol must be metabolized into ACD, has been collected by different approaches including catalase manipulations (Aragon et al, 1985, 1991; Aragon and Amit, 1992), the use of alcohol dehydrogenase (ADH) (Amit, 1977; Brown et al, 1979; Smith et al, 1984; Quertemont and De Witte, 2001; Peana et al, 2008a) or ALDH inhibitors (Amit, 1977; Spivak et al, 1987a,b; Suh et al, 2006), the use of knock-out mice for the CYP2E1 isoform (Suh et al, 2006; Correa et al, 2009a) and the use of lentiviral vectors to silence the cell genome encoding for catalase or ADH synthesis (Karahanian et al, 2011). These approaches generated a large number of studies, summarized in comprehensive reviews (Quertemont et al, 2005; Correa et al, 2012), showing that locomotor (Escarabajal and Aragon, 2002; Martí-Prats et al, 2010; Ledesma and Aragon, 2012), anxiolytic (Correa et al, 2008; Escrig et al, 2012) and, in particular, motivational (Peana et al, 2008a,b, 2009, 2010a) properties of ethanol could be prevented by inhibiting either its peripheral and central metabolism or by ACD inactivation. Notably, two further issues, one related to the questioned ability of ACD to cross the blood brain barrier [see Correa et al (2012) for an extensive discussion on this issue] and another related to the role of enhanced ethanol plasma concentrations that may in turn reach the brain, require to be dealt with while taking into consideration the consequences of blockade of ethanol peripheral metabolism.…”

Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats

“…Furthermore, behavioral studies indicated that the inhibition of several effects of ethanol by cyanamide is mediated by its effects on brain catalase (e.g. SanchisSegura et al 1999;Escarabajal and Aragon 2002). Therefore, the inhibition of brain catalase might be involved similarly in the potentiation of ethanol-induced CTA by cyanamide.…”