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Zhou’s research focuses on the roles of central arginine vasopressin/V1b receptor, proopiomelanocortin (POMC)/mu opioid receptor (MOR), dynorphin/kappa opioid receptor (KOR), and endocannabinoid systems in alcohol addiction.

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

Using knock-in mice with human FAAH C385A SNP, Zhou and colleagues at Weill Cornell Medicine found that FAAHA/A mice have 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.

Zhou found that nalfurafine, a clinically utilized KOR agonist, dose-dependently reduces excessive alcohol consumption and prevents “relapse” drinking. Nalfurafine combined with naltrexone or nalmefene showed a greater reduction than any drug alone, suggesting new strategies for the development of therapeutics for alcoholism.

Zhou and his collaborators at the University of Guelph in Canada found that bupropion combined with naltrexone reduces “binge” alcohol drinking.

Finally, using transgenic mice with hypothalamic-specific POMC deficiency, Zhou and colleagues at the University of Michigan found that POMC-enhancer deletion decreased “relapse” drinking, suggesting that hypothalamic POMC plays essential roles in alcohol relapse.