Ethanol intake and ethanol-induced locomotion and locomotor sensitization in Cyp2e1 knockout mice.
OBJECTIVE
It has been shown that acetaldehyde is an active metabolite of ethanol with central actions that modulate behavior. Catalase has been proposed as the main enzyme responsible for the synthesis of acetaldehyde from ethanol in the brain. Recent studies, however, suggest that cytochrome, in particular the isoform P450 2E1, can also contribute to the central metabolism of ethanol.


METHODS
Cytochrome P4502E1 knockout (KO) mice were used to assess the involvement of this isoenzyme in some of the acute and chronic behavioral effects of ethanol. Ethanol-induced locomotion, locomotor sensitization, and voluntary ethanol intake were evaluated in cytochrome P4502E1 KO mice and their wild-type (WT) counterparts.


RESULTS
Spontaneous locomotion in KO mice was lower than that seen in the WT mice. Acute administration of ethanol (1.5 g/kg, intraperitoneally) increased locomotion to a similar extent in both strains of mice. Repeated intermittent administration of ethanol produced sensitization in both strains, but it was very subtle in the KO mice compared with the effect in the WT mice. KO mice showed a reduction in preference for ethanol intake at low concentrations (4-8% v/v). Interestingly, western blot for catalase in the brain and liver showed that KO mice had higher levels of catalase expression compared with WT mice.


CONCLUSIONS
These results show some impact of the mutation on ethanol-induced sensitization and on voluntary ethanol preference. The lack of a substantial impact of the mutation can be explained by the fact that the KO animals have a compensatory increase in catalase expression compared with WT mice, therefore possibly showing alterations in the formation of acetaldehyde after ethanol administration.
Correa
Mercè
M
Department of Psicobiology, University Jaume I, Castelló, Principe Felipe Institute, Valencia, Spain. correa@psb.uji.es
Viaggi
Cristina
C
Escrig
Miguel A
MA
Pascual
María
M
Guerri
Consuelo
C
Vaglini
Francesca
F
Aragon
Carlos M G
CM
Corsini
Giovanni U
GU
D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D008124:Locomotion / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1