BEHAVIORAL, GENETIC AND NEUROCHEMICAL ASPECTS OF ALCOHOL PREFERENCE OF MICE

Abstract Certain taxa including apes and rodent species and strains exhibit high voluntary ethanol consumption. In rodents which show marked directional or site preference it is possible to quantify the degree of ethanol-seeking behavior by interplaying the site and alcohol motivation; for example, a mouse which consumes large amount of alcohol as compared with water, even when the former is offered at the aversive site, may be classified as actively attracted to ethanol. Using this paradigm, several categories of alcohol-seeking behavior could be established and their occurrence evaluated in C57B1/6J, C3H and CF1 mice, both on inter- and intra-stiain level. In confirmation of earlier data dealing with voluntary consumption we could show that adult C57B1/6J mice showed high degree of active attraction while C3H and CF1 adults exhibited high degree and incidence of aversion; furthermore, each strain represented a wide spectrum of individual differences in alcohol behavior. Some results indicate that alcohol attraction depends on the levels and/or turnover of brain serotonin. Individual CF1 mice which show alcohol attraction as compared to alcohol aversion of other CF1 subjects also exhibit relatively high serotonin level; as ethanol consumption causes a decrease in serotonin levels, alcohol attraction may be related to the reinforcing properties of the normalization of serotonin levels. Data are also presented that suggest that abnormally high serotonin levels may be induced in certain CF1 mice by the experimental paradigm. In this context, our results as well as those of others indicate that “emotional” traits of mouse behavior may be related to alcohol attraction; this was true with the C57B1/6J strain as compared to CF1 strain. Similarly, “regressive behavior” (low rank based on the outcome of fighting episodes of individual CF1 mice) seems to be related to high drinking, while improvement in rank may shift this behavior to ethanol aversion. In agreement with this speculation changes in serotonin (rather than norepinephrine) occur 24 and 48 hours following alcohol withdrawal. Furthermore, strains (such as C57B1/6J) which are relatively attracted to ethanol show high brain serotonin concentrations, comparable to those of individual CF1 mice which are “heavy drinkers”. It must be emphasized that strains in question differ with respect to many neurotransmitters besides serotonin. Finally, the age-related onset of alcohol attraction among CF1 mice seems to follow the post-natal peaking of serotonin levels. Our results show also that alcohol behavior is a developmental process. Post-natally, all strains show early onset of alcohol attraction followed by that of aversion. In the case of the non-drinking C3H and CF1 strains aversive behavior appears early and includes most of the mice; in drinking C57B1/6J mice aversion appears relatively late and percentage of aversives is relatively low. Individual CF1 mice differ as to the patterns of development of aversion. Interesting terminal phase of increased ethanol attraction was noticed on intra- as well as on inter-strain level. It is conceptualized that the inter- and intra-strain ethanol attraction is dependent on delay in a maturation process. Such delay may reflect general developmental patterns of functional and behavioral parameters; e.g. alcohol-attracted individual CF1 mice exhibit a delay in the development of decreased fluid consumption/gram weight. Also, the delay may reflect changes in neurotransmitters or their ratio.