The effect of genetic background on functional brain networks activated in response to cocaine using whole brain imaging

About This Grant

ABSTRACT Approximately 5.3 million individuals in the United States used cocaine in the last year and 1.4 million met the diagnostic criteria for Cocaine Use Disorder (CUD). CUD is a devastating disease with significant consequences for affected individuals, their families and society, yet there are currently no FDA-approved treatments. Recently developed methodologies in tissue clearing and cell-specific labelling allow for unbiased interrogation of brain regions that are activated in response to cocaine and other drugs. These imaging techniques can advance our understanding of neural processes that contribute to addiction by identifying functional brain networks that are perturbed in response to repeated drug exposures. Previous studies have successfully used whole-brain c-Fos mapping along with functional connectivity analysis in cleared brains to identify patterns of activity that change in response to cocaine, methamphetamine, opiates and alcohol. These studies only considered a single genetic background, however, which could limit translational significance. Only about one in five people who use cocaine will go on to develop CUD suggesting that individual differences, including genetic factors, contribute to risk. However, little is known about genetic and neural mechanisms that drive the transition from cocaine use to CUD and why some individuals are more at risk than others. Identifying brain networks that are differentially activated in response to cocaine in genetically heterogeneous mice would inform our understanding of how individual genetic differences contribute to drug response and reward. These studies will reveal interactions between drug exposure and genetic background that could uncover unique mechanisms that increase risk for CUD and lead to novel targets for prevention and treatment.