Study On The Social Behavioral Differences And Molecular Mechanisms Of Mice With Different Alcohol Drinking Preferences

Background and objective:Alcohol use is a common public health problem worldwide,and alcohol use may cause a series of physical and mental health problems.There are significant individual differences in the development of pathological drinking,and only a small number of people develop from drinking preference to pathological drinking.Therefore,paying attention to the behavioral characteristics of individuals with different drinking preferences is very important for understanding the development process of pathological drinking.Previous studies have shown that there is a complex interrelationship between alcohol use and social behavior,but the impact of drinking preference on social behavior and the neural mechanisms are still unclear.Therefore,the focus of this study was to investigate whether differences in social behavior in mice with different drinking preferences were related to changes in microglial changes and related receptor expression in the prefrontal cortex and nucleus accumbens.Therefore,studying the relationship between drinking and social behavior can better understand the characteristics of individual social behavior after drinking,and provide reference for future clinical research on the neural mechanism of excessive drinking and alcohol addiction prevention.Subject and methods:In this study,C57BL/6J male mice were used to establish a two-bottle drinking model,and high drinking preference(HAP)and low drinking preference(LAP)mice were screened out.Study 1 used the three-chamber social behavior test to compare the social ability of LAP and HAP mice,and used the open field test,elevated plus maze test,and new object recognition experiments to exclude the effects of anxiety,depression,and short-term memory on the social behavior of mice with different drinking preferences.Influence.The number of c-Fos neurons per unit area in the medial prefrontal cortex(m PFC)and nucleus accumbens(NAc)of LAP and HAP mice was determined by protein immunofluorescence,that is,the number of activated neurons.Study 2 explored the changes in the number and morphology of activated microglial cells per unit area in the m PFC and NAc brain regions of LAP and HAP mice.The expressions of GABA_Breceptors and NMDA-related receptors in m PFC and NAc were determined by Western blot.Result:Research 1 found:(1)HAP and LAP mice were screened out by two-bottle alcohol drinking model.Control(Con),LAP,and HAP mice showed no significant difference in sociability;LAP mice scored higher on the Social Novelty Index.(2)There was no statistical difference in open field test,elevated plus maze test and novel object recognition test between LAP,HAP and Con groups.(3)After the social behavior test,the expression of c-Fos in the prelimbic cortex(Pr L)and Infralimbic area(IL)of LAP mice increased significantly.(4)There is a significant correlation between the number of activated neurons in the Pr L and IL and the social novelty index.Research 2 found:(1)In both Pr L and IL brain region,the number of microglia in HAP mice increased and the ratio of microglial cell body to area increased,and the area of microglial processes in HAP mice decreased;in the IL,LAP and HAP mice had shortened branch lengths of microglia.(2)In the NAc,the number of microglia increased and the ratio of cell body to area increased in HAP mice,and the area of microglial processes decreased.(3)In the m PFC,the expression ofγ-aminobutyric acid B(GABA_B)receptor 2 in HAP mice was significantly decreased.Compared with HAP,LAP mice showed significantly increased NMDA receptor 2A subunit(NR2A)expression and glutamate transporter 2(EAAT2)receptor expression.(4)In the NAc,the expression of GABA_BR2 was significantly decreased in HAP mice compared with Con and LAP mice.Conclusion:Different alcohol-preferring mice exhibit significant differences in social novelty,which may be associated with the activation and morphological changes of astrocytes in the m PFC and NAc,as well as changes in the expression of inhibitory GABA_B receptors and excitatory NMDA receptors in astrocytes in the m PFC.