Tyler A Roy, Jason A Bubier, Price E Dickson, Troy D Wilcox, Juliet Ndukum, James W Clark, Stacey J Sukoff Rizzo, John C Crabbe, James M Denegre, Karen L Svenson, Robert E Braun, Vivek Kumar, Stephen A Murray, Jacqueline K White, Vivek M Philip, Elissa J Chesler
Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug-use phenotypes, thereby implicating shared genetic mechanisms. High-throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes. We used this strategy in two rounds of candidate prioritization in which we identified 33 drug-use candidate genes based upon predisposing drug-naïve phenotypes and ultimately validated the perturbation of 22 genes as causal drivers of substance intake...
January 2, 2024: Genes, Brain, and Behavior