Development of an animal model of alcohol withdrawal and further studies of alcohol and Na,K-ATPase
Chronic ethanol exposure impairs all organs and systems. There is no complete animal model for human alcoholism. Development of an animal model specific for traits of human alcoholism is therefore important. Outbred Long/Evans (L/E) prepubertal rats were found to be an excellent model for alcohol withdrawal seizure in humans, due to the following advantages: (1) They are highly sensitive to ethanol and the withdrawal syndrome is easily elicited. (2) Only short exposure times are needed to induce withdrawal seizures. (3) The severity of withdrawal syndrome is age-related. Younger animals show more severe symptoms. (4) They are commercially available with no need for specifically bred lines. (5) They are genetically specific, for other commonly used rat strains do not show extreme withdrawal signs. Metabolism of ethanol was compared between immature and mature rats in vivo (measurement of blood ethanol concentration) and in vitro (alcohol dehydrogenase activity). The ethanol metabolic rate in immature rats was faster than that in mature rats. Thus, the pronounced effect of chronic ethanol consumption was not due to a deficit in ethanol elimination that exposes immature L/E rats to higher blood ethanol concentrations.^ The effects of chronic ethanol consumption on cardiac Na,K-ATPase activity in rats was studied. The enzyme activity was inhibited 50% after chronic ethanol treatment. This reduction was not observed in cultured rat heart cells. The results suggest that ethanol indirectly inhibits cardiac Na,K-ATPase activity.^ A protocol was designed to isolate and characterize a putative regulatory peptide for Na,K-ATPase. However, no single peptide was found to be responsible for the alcohol sensitive inhibition of Na,K-ATPase as proposed previously. Instead, a lipid-like fraction found from rat brain inhibited the enzyme. The ionic environment may be a more important factor in determining the effects of ethanol on this enzyme.^ Some of the biochemical and behavioral changes caused by chronic ethanol exposure are reversible after ethanol was removed (i.e., body weight deficit, Na,K-ATPase activity in cerebral cortex, fatty liver, alcohol dehydrogenase activity and withdrawal syndrome). L/E rats previously exposed to ethanol preferred to drink water when given a two-bottle choice of water and ethanol. However, naive rats showed no drinking preference in this situation. ^
Biology, Animal Physiology|Chemistry, Biochemistry|Health Sciences, Pathology
"Development of an animal model of alcohol withdrawal and further studies of alcohol and Na,K-ATPase"
Dissertations and Master's Theses (Campus Access).