title: Induction of brain CYP2E1 changes the effects of ethanol on dopamine release in nucleus accumbens shell.
abstract: CYP2E1 is an important enzyme involved in the brain metabolism of ethanol that can be induced by chronic consumption of alcohol. Recent works have highlighted the importance of this system in the context of the behavioural effects of ethanol. Unfortunately, the underlying neurochemical events for these behavioural changes, has not been yet explored. In this work, we have started this exploration by analyzing the possible changes in the neurochemical response of the mesolimbic system to ethanol after pharmacological induction of brain CYP2E1. We have used the dopamine extracellular levels in nucleus accumbens (NAc) core and shell, measured by means of microdialysis in vivo, as an index of the effects of ethanol. Acetone 1% in the tap water was used to induce brain CYP2E1. Efficacy of the induction protocol was assessed by immunoblotting. Intravenous administration of 1.5 g/kg of ethanol in control rats provoked a significant increase of the dopamine levels in both the core (up to 127% of baseline) and the shell (up to 122% of baseline) of the NAc. However, the same dose of ethanol in acetone-treated rats only increased the dopamine extracellular levels in the core (up to 142% of baseline) whereas dopamine levels in the shell subregion remain unaltered relative to baseline. The results of this study indicate that induction of CYP2E1 changes the response of the mesolimbic system to ethanol in a region-dependent manner. Two hypotheses are postulated to explain the observed effects.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Valencia, Avda Vicente Andrés Estellés s/n, 46100 Burjassot, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Hipólito
authors.forename: María J
authors.initials: MJ
authors.lastname: Sánchez-Catalán
authors.forename: Ana
authors.initials: A
authors.lastname: Polache
authors.forename: Luis
authors.initials: L
authors.lastname: Granero
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D004298:Dopamine