Individual roles of brain and serum alcohol dehydrogenase isoforms in regulation of alcohol consumption in SPF Wistar rats

Autor: Nikita A. Mitkin, O. A. Averina, Maxim L. Lovat, Vsevolod V. Pavshintsev, Ekaterina A. Kushnir, Olga Y. Frolova
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Alcohol Drinking
Experimental and Cognitive Psychology
Alcohol
Motor Activity
Antibodies
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
Reflex
Righting
0302 clinical medicine
Dopamine
Internal medicine
medicine
Animals
Neurotransmitter metabolism
Horses
Ethanol metabolism
Enzyme Inhibitors
Rats
Wistar
Stupor
Alcohol dehydrogenase
Fomepizole
Ethanol
biology
Dose-Response Relationship
Drug
urogenital system
Vaccination
Acetaldehyde
Alcohol Dehydrogenase
Brain
Metabolism
Recombinant Proteins
Specific Pathogen-Free Organisms
Isoenzymes
030104 developmental biology
Endocrinology
chemistry
biology.protein
Exploratory Behavior
Pyrazoles
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Biomarkers
medicine.drug
Zdroj: Physiologybehavior. 179
ISSN: 1873-507X
Popis: Alcohol dehydrogenases (ADH) are key enzymes of ethanol metabolism that mediate its oxidation to acetaldehyde. ADHs are also able to oxidize some types of neurotransmitters such as dopamine, serotonin and norepinephrine. Increased level of ADHs activity, induced by chronic alcohol consumption, is presumably associated with disturbed neurotransmitters metabolism that leads to stable alcohol craving. As earlier reported, intraperitoneal administration of 4-methilpirasole (non-specific inhibitor of ADHs) has shown to provide a short-term anti-alcoholic effect, but individual roles of ADH isoforms in this process were still unclear. The aim of this work was to study the roles of brain and serum ADH isoforms in alcohol consumption and neurotransmitter metabolism in the rats. In the study we used specific-pathogen-free (SPF) Wistar rats chronically alcoholized with 15% ethanol. 4-methilpirasole intranasal administration in small doses led to local inhibition of ADH III activity in the brain estimated by spectrophotometric assay. It correlated with dose-dependent reduction of dopamine concentration and increased level of its metabolic products in the brain but did not influence alcohol consumption. These data allowed us to propose an important role of brain ADHs (predominantly ADH III) in metabolism of dopamine in chronically alcoholized rats but not in regulation of alcohol consumption. To evaluate the role of serum ADH isoforms we immunized the rats with recombinant horse ADH that led to production of high levels of cross-reactive anti-ADH antibodies verified by ELISA assay. Immunization led to 30% decrease in alcohol consumption and recovery of general behavioral parameters such as motor activity, anxiety and depression level. At the same time active immunization did not cause any impairments in animal blood composition. We can conclude that immunization against ADHs appeared to be a safe way to decrease alcohol consumption that could be possibly associated with neurotransmitters metabolism correction.
Databáze: OpenAIRE
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