Is catalase involved in the effects of systemic and pVTA administration of 4-methylpyrazole on ethanol self-administration?
| Autor: | Simona Porru, Pier Andrea Serra, Michela Rosas, Francesca A. Pintus, Gaia Giovanna Maria Rocchitta, Federico Bennardini, Alessandra Tiziana Peana, Gianfranco Bazzu, Elio Maria Gioachino Acquas |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Health (social science) Antidotes Self Administration Pharmacology Toxicology Biochemistry 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine medicine Animals Rats Wistar Saccharin Injections Intraventricular Alcohol dehydrogenase Fomepizole Ethanol biology Ventral Tegmental Area Acetaldehyde Hydrogen Peroxide General Medicine Metabolism Catalase Rats 030227 psychiatry Ventral tegmental area medicine.anatomical_structure Neurology chemistry Systemic administration biology.protein Conditioning Operant Pyrazoles 030217 neurology & neurosurgery |
| Zdroj: | Alcohol. 63:61-73 |
| ISSN: | 0741-8329 |
| Popis: | The oxidative metabolism of ethanol into acetaldehyde involves several enzymes, including alcohol dehydrogenase (ADH) and catalase-hydrogen peroxide (H 2 O 2 ). In this regard, while it is well known that 4-methylpyrazole (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 H 2 O 2 , a mechanism that may indirectly affect catalase whose enzymatic activity requires H 2 O 2 . 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 H 2 O 2 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 H 2 O 2 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-H 2 O 2 system activity as a result of a reduction of H 2 O 2 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. |
| Databáze: | OpenAIRE |
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