Evaluating the Effect of Chronic Alcohol, Cocaine, and Co-Administration on Endogenous Adult Neural Stem Cell Survival, Differentiation, and Proliferation

Cocaine and alcohol are two of the most commonly co-abused substances, and the third most fatal drug combination. Efforts in drug addiction research primarily focus on preventing or stopping abuse; however little work is being done to reverse brain damage incurred by chronic drug abuse. Neural stem cells (NSCs) are a promising target to stimulate brain recovery, yet little is known about the effect of long term co-abuse of alcohol and cocaine on this cell population. Additionally, sex differences in NSC behavior following chronic drug abuse have yet to be evaluated. This is the first study to evaluate regional and sex-dependent responses of endogenous adult NSCs to chronic treatment with alcohol and cocaine. I sought to elucidate the response of adult endogenous NSCs to chronic alcohol and cocaine treatment using an inducible lineage tracing mouse model. This model enables us to trace a given population of NSCs in response to drug treatment. In this dissertation I will briefly discuss the role of adult NSCs in homeostatic and pathological conditions, as well as recent technological advances for studying NSCs. Next I will describe findings which show regional, temporal, and sex dependent responses of endogenous NSCs to alcohol; specifically changes in survival and neurogenesis. Finally, I will summarize data interrogating the impact of chronic cocaine, alcohol, and co-administration on NSC survival and differentiation, and how these changes correlate with cognitive and behavioral changes.