Developmental And Gender Differences In The Acquisition Of Alcohol Conditioned Place Preference In Mice And The Influences Of Stress

Objectives: Alcohol addiction and dependence have become an increasingly serious health and social problem. Psychological, biological and environmental factors all influence the development of addiction. Data from clinic shows that there are behavioral and pathopsysiological differences between adolescence and adult in alcohol addiction and dependence as well as other drugs. Many studies of animal also indicate that immature rodents respond differently to alcohol and other addictive agents compared with those of mature. The outcome of studies involving gender differences in alcoholism varies according to the different aspects they focus on. A mostly accepted opinion is that female individuals are more sensitive to many effects of alcohol such as rewarding effect and impact property, but less sensitive to the tolerance and withdrawal symptoms. Stress can be a single effective factor in alcohol addiction and dependence. Numerous clinical data suggest that stressful event increase alcohol intake and is a risk for relapse for enhancement of craving during sobriety. In the animal models, stress can sensitize the rewarding effect of alcohol, reinforce the alcohol-induced locomotion, and reinstates alcohol-seeking behavior in relapse. Studies of the effects of stress on alcohol consumption have produced conflicting results including increasing, decreasing or no influencing alcohol addiction of stress exposure have been observed. Conditioned place preference (CPP) paradigm has been widely used to evaluate the rewarding and psychologic dependence property of drug. The purpose of this study was to explore some effective factors on the acquisition of alcohol induced CPP of mice, such as age,sex and stress. Using the mice alcohol CPP model, the present study are examined the effective factors such as age, sex and stress on the acquisition of mice alcohol CPP of different age and gender.Methods: In the experiment 1, after a pre-conditioned procedure, mice were selected and divided into 4 groups which were adolescent-male, adult-male, adolescent-female, adult-female by their age and sex, then divided into 4 sub-groups and trained for a CPP by the administration of alcohol at doses of 2g/kg, 1g/kg, 0.5g/kg and saline respectively. While in the experiment 2 and 3, the above 4 groups were also divided into 4 sub-groups, stress-1w+etOH, stress-1w+NS, stress-1d+etOH, stress-1d+NS, In the experiment 2. All mice had to undergo an uncontrollable stressful procedure (randomly 20 times, 0.6mA electrical foot shock for 10min every day) for 1 day or 1 week before trained for the alcohol CPP. The acquisition of CPP was observed after the training.Results: Both adult male and female groups could express an alcohol CPP at the dose of 2g/kg while both the adolescent ones failed at any doses without any pre-treatments. After a stress procedure, the adolescent groups pre-treated with 7-day but not 1-day stress showed a significant CPP.. However, stress didn't influence the acquisition of low-dose alcohol CPP in adult mice. The present study showed that both adult male and female mice could express an alcohol CPP while both the adolescent ones failed without any pre-treatments. After a stress procedure, the adolescent mice pre-treated with 7-day but not 1-day stress showed a significant CPP. There were no gender differences in the stress-induced alcohol CPP in adolescent mice. However, stress didn't influence the acquisition of low-dose alcohol CPP in adult mice and had no interaction with age and gender in the adult mice. The present study indicated that the age but not gender could influence the acquisition of alcohol CPP and chronic but not acute stress played an important role in the acquisition of alcohol CPP for adolescent mice regardless their gender. Both acute and chronic stress had less effect on the acquisition of low-dose alcohol CPP of the adult mice and no relation to the gender.Conclusion: The present study indicated that adult mice were easier to acquire the alcohol CPP than adolescent ones. 2g/kg might be the preferred dose. In the adolescent groups, chronic but not acute or single stress played an important role in the acquisition of alcohol CPP. While in the adult groups, both chronic and acute stress had no effects in the low-dose alcohol CPP.