The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H2O2). In this regard, while it is well known that 4-m ethylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of H2O2, a mechanism that may indirectly affect catalase whose enzymatic activity requires H2O2. The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.p. [intraperitoneal]) and local (into the posterior ventral tegmental area, pVTA) administration of 4-MP on oral ethanol self-administration, and 2) to assess ex vivo whether or not systemic 4-MP affects liver and brain H2O2 availability. The results show that systemic 4-MP reduced ethanol but not acetaldehyde or saccharin self-administration, and decreased the ethanol deprivation effect. Moreover, local intra-pVTA administration of 4-MP reduced ethanol but not saccharin self- administration. In addition, although unable to affect basal catalase activity, systemic administration of 4-MP decreased H2O2 availability both in liver and in brain. Overall, these results indicate that 4-MP interferes with ethanol self-administration and suggest that its behavioral effects could be due to a decline in catalase-H2O2 system activity as a result of a reduction of H2O2 availability, thus highlighting the role of central catalase-mediated metabolism of ethanol and further supporting the key role of acetaldehyde in the reinforcing properties of ethanol.

Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration? / Peana, Alessandra Tiziana; Pintus, Francesca A.; Bennardini, Federico; Rocchitta, Gaia Giovanna Maria; Bazzu, Gianfranco; Serra, Pier Andrea; Porru, Simona; Rosas, Michela; Acquas, Elio. - In: ALCOHOL. - ISSN 1873-6823. - 63:(2017), pp. 61-73. [10.1016/j.alcohol.2017.04.001]

Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration?

PEANA, Alessandra Tiziana;BENNARDINI, Federico;ROCCHITTA, Gaia Giovanna Maria;BAZZU, Gianfranco;SERRA, Pier Andrea;
2017

Abstract

The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H2O2). In this regard, while it is well known that 4-m ethylpyrazole (4-MP) acts by inhibiting ADH in the liver, little attention has been placed on its ability to interfere with fatty acid oxidation-mediated generation of H2O2, a mechanism that may indirectly affect catalase whose enzymatic activity requires H2O2. The aim of our investigation was twofold: 1) to evaluate the effect of systemic (i.p. [intraperitoneal]) and local (into the posterior ventral tegmental area, pVTA) administration of 4-MP on oral ethanol self-administration, and 2) to assess ex vivo whether or not systemic 4-MP affects liver and brain H2O2 availability. The results show that systemic 4-MP reduced ethanol but not acetaldehyde or saccharin self-administration, and decreased the ethanol deprivation effect. Moreover, local intra-pVTA administration of 4-MP reduced ethanol but not saccharin self- administration. In addition, although unable to affect basal catalase activity, systemic administration of 4-MP decreased H2O2 availability both in liver and in brain. Overall, these results indicate that 4-MP interferes with ethanol self-administration and suggest that its behavioral effects could be due to a decline in catalase-H2O2 system activity as a result of a reduction of H2O2 availability, thus highlighting the role of central catalase-mediated metabolism of ethanol and further supporting the key role of acetaldehyde in the reinforcing properties of ethanol.
Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration? / Peana, Alessandra Tiziana; Pintus, Francesca A.; Bennardini, Federico; Rocchitta, Gaia Giovanna Maria; Bazzu, Gianfranco; Serra, Pier Andrea; Porru, Simona; Rosas, Michela; Acquas, Elio. - In: ALCOHOL. - ISSN 1873-6823. - 63:(2017), pp. 61-73. [10.1016/j.alcohol.2017.04.001]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/177193
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