Recently, Dr. Zhou’s research in the Kreek laboratory has focused on the role of endogenous opioid neuropeptides, β-endorphin, dynorphin, and their central receptors, especially the μ (MOR) and κ (KOR) opioid receptor subtypes, in drug addiction. Evidence obtained in humans and rodents indicates that β-endorphin — encoded by the proopiomelanocortin (POMC) gene — is critical in regulation of alcohol drinking behavior. Using genetically selected Sardinian alcohol-preferring (sP) rats, he and Giancarlo Colombo at the Institute of Neuroscience in Italy have found that chronic voluntary alcohol drinking increased POMC gene expression in the hypothalamus of sP rats. Using transgenic mice with hypothalamic-specific deletion of POMC expression, he and Malcolm Low at the University of Michigan, have found that the POMC-deficient mice had less alcohol intake and blunted “relapsing” drinking after chronic alcohol self-administration, suggesting that hypothalamic POMC plays essential roles in compulsive drinking behavior. In collaboration with Francesco Leri at the University of Guelph in Canada, he has found that amygdalar dynorphin gene expression levels were increased after acute stress in heroin withdrawn rats, and selective KOR antagonists dose-dependently blocked stress-induced reinstatement of heroin-seeking behavior. To explore the potential of functionally selective KOR agonists with fewer side effects in alcoholism treatment models, he and Thomas Prisinzano at the University of Kansas are actively testing novel KORs in mouse alcohol drinking behavior.