Long-term inhibition of ethanol intake by the administration of an aldehyde dehydrogenase-2 (ALDH2)-coding lentiviral vector into the ventral tegmental area of rats
Author
dc.contributor.author
Karahanian, Eduardo
Author
dc.contributor.author
Rivera Meza, Mario
Author
dc.contributor.author
Tampier de Jong, Lutske
Author
dc.contributor.author
Quintanilla González, María Elena
Author
dc.contributor.author
Herrera-Marschitz Muller, Mario
Author
dc.contributor.author
Israel Jacard, Yedy
Admission date
dc.date.accessioned
2015-08-14T15:25:08Z
Available date
dc.date.available
2015-08-14T15:25:08Z
Publication date
dc.date.issued
2014
Cita de ítem
dc.identifier.citation
Addiction Biology, 20, 336–344
en_US
Identifier
dc.identifier.issn
1369-1600
Identifier
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DOI: 10.1111/adb.12130
Identifier
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https://repositorio.uchile.cl/handle/2250/132745
General note
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Artículo de publicación ISI
en_US
Abstract
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Previous studies suggest that acetaldehyde generated from ethanol in the brain is reinforcing. The present studies tested
the feasibility of achieving a long-term reduction of chronic and post-deprivation binge ethanol drinking by a single
administration into the brain ventral tegmental area (VTA) of a lentiviral vector that codes for aldehyde
dehydrogenase-2 (ALDH2), which degrades acetaldehyde. The ALDH2 gene coding vector or a control lentiviral vector
were microinjected into the VTA of rats bred for their alcohol preference. In the chronic alcohol administration model,
naïve animals administered the control vector and subsequently offered 10% ethanol and water ingested 8–9 g
ethanol/kg body weight/day. The single administration of the ALDH2-coding vector prior to allowing ethanol availability
reduced ethanol drinking by 85–90% (P < 0.001) for the 45 days tested. In the post-deprivation binge-drinking
model, animals that had previously consumed ethanol chronically for 81 days were administered the lentiviral vector
and were thereafter deprived of ethanol for three 7-day periods, each interrupted by a single 60-minute ethanol
re-access after the last day of each deprivation period. Upon ethanol re-access, control vector-treated animals consumed
intoxicating ‘binge’ amounts of ethanol, reaching intakes of 2.7 g ethanol/kg body weight in 60 minutes. The
administration of the ALDH2-coding vector reduced re-access binge drinking by 75–80% (P < 0.001). This study
shows that endowing the ventral tegmental with an increased ability to degrade acetaldehyde greatly reduces chronic
alcohol consumption and post-deprivation binge drinking for prolonged periods and supports the hypothesis that
brain-generated acetaldehyde promotes alcohol drinking.
en_US
Patrocinador
dc.description.sponsorship
FONDECYT Grant Nos.1130012,
1095021 and 1120079 and the Millennium Scientific
Initiative P09–015-F
Long-term inhibition of ethanol intake by the administration of an aldehyde dehydrogenase-2 (ALDH2)-coding lentiviral vector into the ventral tegmental area of rats