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Zhou’s research in Mary Jeanne Kreek’s lab focuses on the roles of central arginine vasopressin/V1b receptor, endorphin/mu opioid receptor (MOP-r), dynorphin/kappa opioid receptor (KOP-r), and cannabinoid systems in drug addiction.

Using genetically selected Sardinian alcohol-preferring rats, Zhou and colleagues at the Institute of Neuroscience in Italy have found that pharmacological blockade of V1b receptor attenuates alcohol drinking in a rat model of human alcoholism. A phase II clinical trial with colleagues at the National Institute on Alcohol Abuse and Alcoholism found that V1b antagonists reduce alcohol relapse in alcohol-dependent patients, especially in ones experiencing high stress.

In another study, using transgenic mice with hypothalamic-specific deletion of endorphin/proopiomelanocortin (POMC) expression, Zhou and colleagues at the University of Michigan have found that POMC-deficient mice have decreased “relapse” drinking after escalated alcohol intake, suggesting that hypothalamic endorphins play essential roles in alcohol relapse via an endorphin/MOP-r–mediated mechanism.

To explore the potential of functionally selective KOP-r agonists with fewer side effects in alcoholism treatment, Zhou and colleagues at the University of Kansas are actively testing novel Salvinorin A analogs in alcohol dependent-like drinking behaviors in mice. Zhou and colleagues at the University of Guelph in Canada have found that either V1b or KOP-r antagonists dose-dependently block stress-induced heroin-seeking behavior. Finally, using knock-in mice with human FAAH C385A SNP, Zhou and colleagues at Weill Cornell Medicine have found that FAAHA/A mice had greater alcohol intake than FAAHC/C mice, consistent with clinical reports that human FAAHA/A carriers have higher alcohol intake and more severe alcohol dependency.