Zheng-Ming Ding, Ph.D.
Assistant Research Professor, Psychiatry
Ph.D., Indiana University (2003-2008)
Postdoctoral, Indiana University (2008-2012)
Neurobiology of alcohol abuse and alcohol-nicotine poly-drug abuse.
Alcohol use disorders (AUDs) are among the most prevalent psychiatric diseases around the world and there is strong demand for effective pharmacological therapeutics. Despite extensive research over several decades, the neurobiology of AUDs remains elusive. Our work has been focusing on identifying neuro-circuits and neurochemical substrates within the central nervous system that may underlie the reinforcing and rewarding effects of ethanol. A series of intra-cranial self-administration (ICSA) studies have pointed to the meso-cortico-limbic (MCL) system (including the ventral tegmental area, nucleus accumbens, and medial prefrontal cortex) as neuro-anatomical substrates that directly mediate the reinforcing effects of ethanol. Activation of dopamine, serotonin, GABA receptors appears to be involved in these effects. In addition, another series of studies have indicated that chronic alcohol exposure produces adaptive changes in dopamine and glutamate neurotransmission within the MCL system at both pre- and post-synaptic levels. These changes alter the responsiveness of this system to alcohol and may contribute to the maintenance of and relapse to alcohol abuse.
Alcohol drinking is frequently correlated with high rates of tobacco smoking. Both human and rodent research suggests an important role of nicotine in the development of alcohol abuse and addiction. Our work shows that nicotine and ethanol produce cross-sensitization within the meso-limbic dopamine system and augment dopamine response to subsequent drug exposure. In addition, on-going studies in our lab are characterizing brain sites and neurochemical mechanisms, as well as other possible factors (e.g., cotinine, the major metabolite of nicotine), in the development of alcohol-nicotine co-abuse.
Selected Recent Publications:
Ding ZM, Oster SM, Hall SR, Engleman EA, Hauser SR, McBride WJ, Rodd RA (2011) The stimulating effects of ethanol on ventral tegmental area dopamine neurons projecting to the ventral pallidum and medial prefrontal cortex in female Wistar rats: regional difference and involvement of serotonin-3 receptors. Psychopharmacology 216: 245-255.
Ding ZM, Katner SN, Rodd ZA, Truitt WA, Sheketha HR, Deehan GA Jr, Engleman EA, McBride WJ (2012) Repeated exposure of the posterior ventral tegmental area to nicotine increases the sensitivity of local dopamine neurons to the stimulating effects of ethanol. Alcohol. 46: 217-223.
Ding ZM, Rodd ZA, Engleman EA, Bailey JA, Lahiri DL, McBride WJ (2013) Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats. Addict Biol. 18: 297-306.
Hauser SR, Bracken AL, Deehan GA Jr, Toalston JE, Ding ZM, Truitt WA, Bell RL, McBride WJ, Rodd ZA (2014) Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine. Addict Biol. 19: 800-811.
McClintick JN, McBride WJ, Bell RL, Ding ZM, Liu Y, Xuei X, Edenburg HJ (2015) Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking. Pharmacol Biochem Behav. 129: 87-96
Ding ZM, Ingraham CM, Rodd ZA, McBride WJ (2015) The reinforcing effects of ethanol within the posterior ventral tegmental area depend upon dopamine neurotransmission to forebrain cortico-limbic systems. Addict Biol. In press