Alcohol Preference In Mice Research Articles

Alcohol dehydrogenase is not a major determinant of alcohol preference in mice

We present evidence that in MRL/Mp mice, difference in one gene affects the activity of alcohol dehydrogenase. MRL/Mp- + show high alcohol dehydrogenase (ADH) activity in the range of that found in C57BL/6, while MRL/Mp-1pr show ADH values in the range of non-drinker strains such as DBA/1, BALB/c, A, SJL, CBA and C3H/He. Voluntary alcohol consumption in MRL/Mp- + is 30–40% higher than that in the MRL/Mp-1pr. However, alcohol preference of both congenic strains is markedly lower than those of C57BL/6 mice. Our findings lead us to conclude that although alcohol dehydrogenase levels do relate to alcohol preference in mice, they are responsible for only a minor fraction of inter-strain differences.

Activity and electrophoretic profiles of liver aldehyde dehydrogenases from mice of inbred strains with different alcohol preference

1. 1. The activity of low K m-aldehyde dehydrogenase (ALDH) in the liver mitochondrial fraction (MT-fraction) from male C57BL/6J strain mice (alcohol preferring) was significantly higher than that from DBA/2 mice (alcohol avoiding). The F 1 hybrids (C57BL/6J × DBA, 2) did not exhibit the intermediate activity to these two strains. 2. 2. Strain differences in liver mitochondrial ALDH isozymcs were observed by isoelectric focusing. C57BL/6J strain had two isozymes at pH 7.1 while DBA/2 had no band at this pH. F 1 hybrid mice had similar two bands with lower density to those of C57BL/6J at pH 7.1. There was no difference in zymograms of the soluble fraction between C57BL/6J and DBA/2 strains. 3. 3. The present results suggest that the difference in alcohol preference of mice may depend on some restricted ALDH isozymes with different pI or electric mobility rather than the enzymatic activity in the liver MT-fraction.

Adrenal hormones and ethanol ingestion in C57BL/Crgl and C3H/Crgl/2 mice

The alcohol consumption of C57BL/Crgl mice decreased significantly when animals of this strain were injected with a solution of 0.2 mg of hydrocortisone acetate (a glucocorticoid) every second day. No such significant decrease in alcohol consumption occurred when C3H/Crgl/2 mice were injected with the same solution daily. When administered a solution of 0.5 mg of deoxycorticosterone acetate (a mineralocorticoid), neither the C57BL/Crgl injected daily or every other day nor the C3H/Crgl/2 injected daily displayed a significant decrease in alcohol consumption. The results indicate possible involvement of glucocorticoids, rather than mineralocorticoids, in the alcohol preference of mice.

Use of genetic to test the potential role of serotonin in alcohol preference

The hypothesis that alcohol preference in mice is influenced by brain serotonin levels was tested using genetic analysis. Alcohol preference and static serotonin content were assessed in C57BL/Ibg (alcohol-preferring) and DBA/2 (alcohol-avoiding) mice, as well as in Fl and F2 generations obtained by crossbreeding. The two parental strains showed dissimilar alcohol preferences but identical concentrations of brain serotonin. Serotonin concentration segregated independently of alcohol preference in the F1 and F2 generations. These data provides strong evidence against the hypothesis that brain serotonin content influences alcohol preference. However, they do not preclude the possibility that differential alcohol influences on serotonin metabolism or turnover rate may result in differing preference for a alcohol.

The use of strain rank orders in assessing equivalence of techniques

In situations where effects of previous testing make it impossible to compare putativety equivalent forms of a behavioral test, inbred strains may be useful. To a considerable extent, animals from an inbred strain represent replicate individuals. Different naive samples from the same strain may be tested in different forms of a test. There is presumptive evidence that the two forms arc assessing similar functions if samples from different strains that differ on the behavior give consistent ordinal rankings. An illustration is given of the use of this approach in assessing methods of measuring alcohol preference in mice.

Effect of Drinking Schedule upon Alcohol Preference in Mice

Effect of Drinking Schedule upon Alcohol Preference in Mice

Factors Underlying Differences in Alcohol Preference Among Inbred Strains of Mice

A conceptual framework is presented that relates behavior pathology, behavior genetics, and the concept of mechanism-specific behavior to the study of alcohol preference of inbred mice as an approach to the understanding of human alcoholism. The programmatic work on alcohol preference of mice is reviewed. Genetic, enzymatic, nutritional, experiential, and stimulus variables are considered. Under appropriate circumstances, voluntary ingestion of sweetened alcohol by appropriate strains is shown to raise rate of mortality and to induce liver pathology similar to that found in some types or stages of human alcoholism.

Genetic and biochemical correlates of alcohol preference in mice.

Certain strains of mice prefer alcohol to water in preference tests whereas others avoid alcohol. This is the behavior which we are trying to explain, and we have formulated several explanatory hypotheses: 1. It was hypothesized that animals of high preference strains metabolize alcohol more quickly than animals of low preference strains. This hypothesis was confirmed. 2. We have asked the question whether there are differences in the activity of liver ADH, the enzyme which catalyzes the rate limiting reaction in alcohol metabolism. We have found that the activity of this enzyme is significantly greater in high than in low preference strains. 3. We have asked whether there are differences in the rate of accumulation of acetaldehyde in high and low preference strains. Tests indicated that significantly greater amounts of blood acetaldehyde accumulate during alcohol metabolism in low than in high preference strains. 4. We have asked whether there are differences in aldehyde dehydrogenase which might account for this differential acetaldehyde accumulation in high and low preference strains. Only an indirect answer is available, but it was found that Antabuse, an inhibitor of aldehyde dehydrogenase, acts differently in high and low preference strains. 5. We have asked whether Antabuse will decrease voluntary consumption of alcohol in normally high or intermediate preference strains. Antabuse was found to decrease voluntary alcohol intake in all strains tested. 6. We have asked whether in mice which show a decrease in alcohol preference with age, liver ADH activity also decreases with time. The answer to this question was affirmative. 7. It was hypothesized that mice which are selectively bred for high and low alcohol preference show a correlated selection response in terms of liver ADH activity. The answer to this question was affirmative; mice selected for high alcohol preference have higher liver ADH activity than mice selected for low alcohol preference. A number of questions were asked about the metabolism of alcohol in different strains of mice in attempting to discover the underlying biochemical reasons for these differences in alcohol preference behavior. In every case the answers make it appear as if we are heading in the right direction. No one, of course, can say whether these differences which we have described are the real answer to why certain mice drink alcohol and others do not. What can be said, however, is that a good start in that direction has been made.