Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.
Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose - response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.
Quintanilla
María Elena
ME
Program of Molecular adn Clinical Pharmacology, Institute of Biomedical Sciences, School of Medicine, University of Chile, Santiago. equintanilla@machi.med.uchle.cl
Tampier
Lutske
L
D000079:Acetaldehyde / Q000097:blood / Q000494:pharmacology; D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics; D001245:Association Learning; D001362:Avoidance Learning; D001921:Brain / Q000201:enzymology*; D003214:Conditioning, Classical; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005973:Glutamine / Q000235:genetics; D007274:Injections, Intraperitoneal; D008297:Male; D017354:Point Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013649:Taste / Q000235:genetics*
D005973:Glutamine; D001120:Arginine; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde