ACETALDEHYDE METABOLISM: DIFFERENCES BETWEEN UChA AND UChB RATS

In order to explore the influence of acetaldehyde (AcH) metabolismon the voluntary ethanol intake of genetically low (UChA) andhigh (UChB) ethanol consumer rats, the AcH disappearance rate(ADR) after incubation with homogenates and subcellular fractionsfrom liver and brain was determined. In addition, the effectof disulfiram pretreatment on AcH metabolism was studied. Maleadult rats of both strains were used. ADR was assayed in totalhomogenates, and in mitochondrial as well as 9000 g supernatantfractions of liver and brain. AcH was measured by gas chromatography.In some experiments, rats were pretreated with disulfiram (300mg/kg po) 24 hr before the studies. The result showed no straindifference in ADR in homogenates or subcellular fractions ofliver from untreated rats, but for disulfiram pretreated ratsa significantly lower decrease of ADR in samples from UChB comparedto UChA rats was observed. This result is consistent with alower peak AcH level in UChB compared to UChA rats after a loadof ethanol (60 mmole/kg ip). Concerning brain homogenates, ahigher ADR was observed in homogenates and crude mitochondrialfractions of UChB than of UChA rats. This difference was notobserved when the incubation was performed without adding NADor in the absence of oxygen. These results provide evidenceof strain differences in mitochondrial AcH metabolism, the natureand origin of which deserve further study.     

BIOLOGICAL SIMILARITIES AND DIFFERENCES BETWEEN RATS GENETICALLY DIFFERENT IN ALCOHOL PREFERENCE

This paper is an inventory of some behavioural, biochemicaland pharmacological similarities and differences between twoinbred strains of Wistar rats differing in voluntary consumptionof ethanol, namely: UChA and UChB with low and high preferencesrespectively for ethanol under conditions involving free choicebetween a 10% (v/v) ethanol solution and distilled water. Thefollowing strain differences were observed: ethanol consumption(UChA<UChB); total water consumption (UChA<UChB); solidfood consumption (UChA>UChB); rate of recovery of ethanollabel in expired CO₂ (UChA<UChB); oxidation of ethanol toacetaldehyde by brain homogenates (UChA>UChB); acetaldehydedisposal by brain homogenates (UChA<UChB); ethanol (90 mmol/kg,i.p.) sleeping-time (UChA<UChB); chronic and acute toleranceto ethanol (UChA developed it, whereas UChB did not); lethaldoses of ethanol (UChA>UChB); recovery rate of the labelof gluconate in expired CO₂ (UChA<UChB); recovery rate ofthe label of fructose in expired CO₂ (UChA<UChB); blood-glucoselevel after glucose (1g/kg, i.p.) load (UChA<UChB). No straindifferences were observed in the rate of recovery in expiredCO₂ of the label of the following substrates: acetate, pyruvate,butyrate, citrate, ribose, glycerol, sorbitol, glucose and galactose.     

EFFECTS OF DIETS DECREASING ETHANOL CONSUMPTION ON ACETALDEHYDE METABOLISM IN UChA AND UChB RATS

It has previously been reported that the introduction of a newissue (D1) of a stock diet (D0) caused a significant decreasein voluntary ethanol consumption in rats of our UChA (low ethanolconsumer) and UChB (high ethanol consumer) strains, and that,after changing to a diet lacking in animal products (D3), ethanolconsumption reached the previous level attained in UChB ratsand exhibited a bimodal distribution in UChA rats in such away that about one-third of these consumed more than 2 ml ofa 10% (v/v) ethanol solution per 100 g of body weight, as didUChB rats. When UChA rats exhibiting high ethanol consumptionand also UChB rats were fed on the D3 diet with a brewer's yeastsupplement, a significant decrease in ethanol intake was observed.Since significant correlations of voluntary ethanol intake toblood acetaldehyde levels, and to hepatic and brain aldehydedehydrogenase (AldDH) activities, have been reported, the effectson these parameters of diet D1 and of supplements of brewer'syeast or disulfiram were studied. Results showed that rats ofboth strains fed on a D1 diet exhibited a significant increasein blood acetaldehyde level after ethanol administration, concomitantwith an inhibition of hepatic and brain AldDH activities anda significant decrease in ethanol intake. Thus, this effectcould be related to a disulfiram-hke activity. The decreasein ethanol intake induced by brewer's yeast was not accompaniedby changes of blood acetaldehyde level after ethanol, nor byinhibition of hepatic AldDH activity in either strain. Nevertheless,a significant inhibition of brain AldDH activity in UChB, butnot in UChA, rats was observed. Thus, the effect of brewer'syeast on ethanol consumption could not be ascribed to a disulfiram-likeactivity of this supplement.the beginning of pregnancy, couldbe toxic for the human placenta and development of the fetus.