A Magnetic Resonance Imaging Study Of Brain Structural Changes In Nicotine Dependence

Tobacco dependence is the most common and widespread drug dependence behavior in human life.Nicotine,the dependence-causing substance in tobacco,have varying degrees of impact on the brain structure and function of smokers.Magnetic resonance imaging(MRI)has been widely used in studies of brain structure and function of smokers for its advantages of non-invasive,high temporal and spatial resolution,which has deepened our understanding of tobacco dependence.However,there are inconsistent results about smokers based on cross-sectional MRI studies due to the differences in the subjects’ age,gender,smoking age,education level and other background factors.And it is difficult to explain the causal relationship between changes in brain structure or function and nicotine dependence.In addition,follow-up histopathology and molecular biology research cannot be conducted on human smokers.Considering the time-varying characteristics of brain functional networks,this study used an animal model of nicotine dependence to exclude the effects of differences in the background of the subjects.A longitudinal design was adopted to explore the characteristics of brain structural changes in nicotine dependence by using MRI,animal behavior and histopathology methods.The specific works are as follows:(1)A nicotine dependent rat model was established by intermittent administration of nicotine with modified mini-osmotic pumps to better imitate human smoking behavior.Based on this model,T2-weighted imaging and histopathological methods were applied to explore the effects of nicotine on gray matter(GM)volume and its possible causes.The results showed that GM volumes within some brain regions,including the prefrontal cortex,insular cortex,striatum,amygdala,hippocampus and ventral tegmental area,were altered.Furthermore,HE staining for the changed brain regions demonstrated that there were varying degrees of morphological and structural changes in cells within those brain regions,which may be the causes of the GM alterations in the rat brains.(2)Using the nicotine-dependent rat model,the effects of nicotine on the macrostructure and microstructure of brain white matter(WM)were investigated by T2-weighted imaging and diffusion tensor imaging.The effects of nicotine on the WM macrostructure of the rat brains mainly involved in the corpus callosum,posterior commissure and cingulate cortex.The effects of nicotine on the WM microstructure of the rat brains mainly involved in the corpus callosum,internal capsule,cingulate cortex,insular cortex,striatum,thalamus and ventral tegmental area,in which the integrity of white matter fibers was affected to some extent.(3)A longitudinal study was conducted in the nicotine-dependent rat model to explore the predictive abilities of brain structural characteristics on subsequent dependence degree and withdrawal recovery ability of nicotine-susceptible rats.Results showed that individuals with greater risk of dependence and more difficult to withdrawal may have the following brain structural characteristics:smaller bilateral prelimbic cortex and left granular insular cortex GM volume,larger right cornuammonis region 1 of hippocampus and left thalamus GM volume;smaller bilateral thalamus WM volume;larger right frontal assocn cortex and right prelimbic cortex fractional anisotropy,smaller corpus callosum,hippocampus,and bilateral thalamus fractional anisotropy.In conclusion,a nicotine-dependent rat model based on intermittent administration of nicotine by mini-osmotic pumps was established and the characteristics of brain structural changes induced by nicotine dependence were investigated by MRI and histopathology methods.These results showed that both GM and WM structures were altered in nicotine dependence,and the innate brain structural characteristics can predict the degree of their subsequent dependence and withdrawal recovery ability.Our results will help to further understand the relationship between nicotine dependence and brain structural changes,and provide data support for the development of targeted smoking cessation programs for smokers in the future.