Chavkin coworkers demonstrated that KOR agonist-induced conditioned place aversion (CPA), an animal model of dysphoria, was mediated by G-protein-coupled receptor kinase 3 (GRK3) and p38 MAP kinase, whereas KOR-mediated analgesic effects were G protein-mediated (Bruchas et al., 2006, 2007, 2011; Land et al., 2009; Bruchas and Chavkin, 2010; Ehrich et al., 2015). Here, GRK3 is linked to dysphoria.