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Research Affiliates

Head shot of Yan Zhou
Yan Zhou, M.D., Ph.D.
Research Associate Professor
Laboratory of the Biology of Addictive Diseases

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.