Effects Of Nicotine Exposure During Adolescence On Ethanol Self-administration In Adulthood And NAChR Expression Of VTA On Wistar Rats

Adolescence is a particularly period for the initiation of drug use. More than 80%of smokers initiated their smoking in Adolescent. Adolescent smoking is one of predictors for alcohol dependence.The nAChR located in VTA may play a vital role in reward mechanisms of ethanol,and may serve as one possible common denominator for the ethanol-nicotine's interaction.The homologous animal model was duplicated in this study.Wistar rats were treated with nicotine during adolescence and ethanol self-administration model was established during adulthood to explore the relationship of nicotine abuse and ethanol abuse and to explore the roles of nAChR in VTA.Objective:To observe the effects of nicotine exposure during adolescence on ethanol self-administration in adulthood,to examine the effect of nicotine exposure during adolescence and ethanol self-administration during adulthood on mRNA expression of some nAChR subunits in VTA.Method:Adolescent Wistar rats were used in this study.Animal received a period of 10 days subcutaneous injections of nicotine(1.0 mg/kg/day salt) or of physiological saline on PN35.Beginning on PN60, part of rats were induced to establish ethanol two-bottle free-choice self-administration by Samson sucrose fading program.Ethanol consumption,alcohol preference and total fluid intake were measured to judge the effect of nicotine treatment,mRNA ofα4,α5,α7 andβ2 nAChR subunit in VTA of each group were measured by Real Time-PCR to judge the effect on mRNA expression of nicotine treatment and ethanol self-administration.Results:There were no differences in Ethanol consumption,alcohol preference and total fluid intake between nicotine and saline treatment during adolescence.The mRNA expressions of each nAChR subunit in VTA showed:1.There were no differences on mRNA expression ofα4,α5,α7 andβ2 nAChR subunit between two exposure groups in VTA.2. There were significant differences at different levels on mRNA expression ofα4,α5,α7 andβ2 nAChR subunits between two alcohol dependence model groups,α4,α5,andβ2 nAChR subunits were up-regulated andα7 nAChR subunit was down-regulated.Factorial ANOVA showed:1.mRNA expression ofα4,α5 were modulated by both factors.2.β2 were modulated by alcohol dependence model factor.3. There were interactions between two factors on mRNA expression ofα5,α7 andβ2 nAChR subunits.Conclusions:1.mRNA expression ofα4,α5,α7 andβ2 nAChR subunits can be modulated by nicotine exposure during adolescence. However,nicotine exposure during adolescence did not increase ethanol intake in Wistar rats during adulthood.This study doesn't verify our theory hypothesis.2.Both nicotine and ethanol affected on nAChR subtype comprisedα4,α5,α7 orβ2 subunits,nAChR subtype comprised ofα4,α5,α7 orβ2 nAChR subunits were involved in the establishing process of alcohol dependence,while it were not of particular importance for establishing alcohol dependence.3.The effects of mRNA expression of nAChR subunits on development of alcohol dependence should combine with genetic diversity.