Distribution and differential induction of CYP2E1 by ethanol and acetone in the mesocorticolimbic system of rat.
OBJECTIVE
The expression of cytochrome P4502E1 (CYP2E1) in the brain has been demonstrated in several regions, nevertheless there is a lack of specific studies on the constitutive expression and induction at the mesocorticolimbic system, the most relevant brain pathway in the context of drug addiction and alcoholism. Hence, we have performed a detailed study of the CYP2E1 expression and induction in three key areas of the mesocorticolimbic system of the rat brain: prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA).


METHODS
Expression levels of CYP2E1 were analyzed by Western blot. The induction of the enzyme in the selected brain areas by chronic acetone (1% v/v acetone in drinking water for 11 days) and ethanol (3 g/kg by gavage for 7 days) was also assessed.


RESULTS
(i) CYP2E1 was expressed in PFC, Nac, and VTA, with the order of magnitude of the levels being VTA approximately PFC > Nac, and approximately 3-13% of it was encountered in liver; (ii) acetone treatment significantly increased CYP2E1 expression in Nac, up to 212% of the control levels, whereas not significant changes were observed in VTA and PFC; (iii) chronic ethanol treatment only resulted in a significant induction of enzyme levels in VTA (124%). A similar enhancement, though not significant, was found to occur in NAc.


CONCLUSIONS
CYP2E1 was present in the mesocorticolimbic system at different levels of expression. Chronic acetone and ethanol treatments are able to increase enzyme levels in specific areas of this system with the pattern of induction of the two agents being different.
Sánchez-Catalán
M José
MJ
Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Valencia, Avda Vicente Andrés Estellés s/n, 46100, Burjassot, Spain.
Hipólito
Lucía
L
Guerri
Consuelo
C
Granero
Luis
L
Polache
Ana
A
D000096:Acetone / Q000494:pharmacology*; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics*; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000096:Acetone; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1