Effects of social housing conditions on ethanol-induced behavioral sensitization in Swiss mice.

RATIONALE: In previous animal model studies, it was shown that drug sensitization is dependent upon physical environmental conditions. However, the effects of social housing conditions on drug sensitization is much less known. OBJECTIVE: The aim of the present study was to investigate the effects of social conditions, through the size of housing groups, on ethanol stimulant effects and ethanol-induced behavioral sensitization in mice. MATERIALS AND METHODS: Male and female Swiss mice were housed in groups of different sizes (isolated mice, two mice per cage, four mice per cage and eight mice per cage) during a six-week period. A standard paradigm of ethanol-induced locomotor sensitization was then started with one daily injection of 2.5 g/kg ethanol for 8 consecutive days. RESULTS: The results show that social housing conditions affect the acute stimulant effects of ethanol. The highest stimulant effects were observed in socially isolated mice and then gradually decreased as the size of the group increased. Although the rate of ethanol sensitization did not differ between groups, the ultimate sensitized levels of ethanol-induced stimulant effects were significantly reduced in mice housed in groups of eight. CONCLUSIONS: These results are consistent with the idea that higher levels of acute and sensitized ethanol stimulant effects are observed in mice housed in stressful housing conditions, such as social isolation.

Voluntary alcohol binge-drinking in adolescent C57Bl6 mice induces delayed appearance of behavioural defects in both males and females.

Adolescence is a developmental period characterized by significant changes in brain architecture and behaviour. The immaturity of the adolescent brain is associated with heightened vulnerability to exogenous agents, including alcohol. Alcohol is the most consumed drug among teenagers, and binge-drinking during adolescence is a major public health concern. Studies have suggested that adolescent alcohol exposure may interfere with the maturation of frontal brain regions and lead to long-lasting behavioural consequences. In this study, by using a slightly modified version of the Drinking in the Dark paradigm, adolescent C57Bl6 mice reach high blood alcohol concentration after voluntary binge-drinking. In order to assess short- and long-term consequences of adolescent alcohol exposure (AAE), a battery of behavioural tests was performed during late adolescence and during adulthood. We showed that AAE had no short-term effect on young mice behaviour but rather increased anxiety- and depressive-like behaviours, as well as alcohol consumption during adulthood. Moreover, alcohol binge-drinking during adolescence dramatically decreased recognition memory performances and behavioural flexibility in both adult males and females. Furthermore, we showed that voluntary consumption of alcohol during adolescence did not trigger any major activation of the innate immune system in the prefrontal cortex. Together, our data suggest that voluntary alcohol binge-drinking in adolescent mice induces a delayed appearance of behavioural impairments in adulthood.

Long-term exposure to daily ethanol injections in DBA/2J and Swiss mice: Lessons for the interpretation of ethanol sensitization.

Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these studies. The first aim of the present study is to better characterize the development and expression of ethanol sensitization after an extended exposure of 45 daily injections. In some previous studies, mice were classified as "respondent" and "resistant" to ethanol sensitization. The second aim of the present study is to test the long-term reliability of such categorizations and the consequences of their use on the interpretation of the ethanol sensitization results. Swiss and DBA/2J female mice received 45 consecutive daily ethanol administrations (respectively 2.5 and 2.0 g/kg) and their locomotor activity was daily recorded to test the development of ethanol sensitization. At the end of the procedure, a challenge test assessed the inter-group ethanol sensitization.The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA/2J mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. Remarkably, ethanol sensitization after such a long daily ethanol treatment resulted in both an upward shift of the magnitude of ethanol stimulant effects and a prolongation of these effects in time (up to 30 minutes). Mice classified as "resistant to ethanol sensitization" according to previous studies developed very significant levels of ethanol sensitization when tested after 45 ethanol injections and are best described as showing a delayed development of ethanol sensitization. Furthermore, mice classified as respondent or resistant to ethanol sensitization also differ in their acute response to ethanol, such that it is difficult to ascertain whether these classifications are specifically related to the sensitization process.