Pilot grants funded January 1, 2015 – December 31, 2017:
Cdk5 is a mu opioid receptor (MOR)-regulated gene that is differentially expressed in the extended amygdala of ethanol-dependent mice voluntarily drinking excessive amounts of ethanol. For this pilot project, we propose to validate the functional implication of cdk5 in the escalation of ethanol self-administration, and to explore which cdk5 downstream effector(s) may mediate this effect. In particular, we will test the hypothesis that cdk5 may contribute to the morphological and functional plasticity associated with alcohol dependence by phosphorylating proteins involved in dendritic remodeling, neurotransmitter release and/or postsynaptic signaling.
Cindy Ehlers & Trina Norden-Krishmar
Mexican American males, particularly those born in the United States, are at greater risk than Caucasians for alcohol-associated morbidity and mortality (Caetano 2003; Caetano et al. 2009). To determine the underlying causes of alcohol use disorders in Mexican Americans, we have performed preliminary evaluation of a cohort of 427 young adult (age 18 - 30) Mexican American men (n=171) and women (n=256). Previously, we have reported a high prevalence of alcohol dependence, and a significant co-morbidity between alcohol dependence and anxiety, affective, conduct/antisocial, and other substance dependence disorders in this cohort (Gilder et al. 2007). Additionally, we have shown that alcohol-use disorders are significantly associated with poorer quality of sleep in this cohort (Ehlers et al. 2010). This pilot study seeks to investigate whether specific genetic variants may be associated with alcohol use disorders, behavioral disorders, and sleep quality phenotypes in this population of young-adult Mexican Americans.
Norden-Krichmar, T. M., Gizer, I. R., Phillips, E., Wilhelmsen, K. C., Schork, N. J., & Ehlers, C. L. (2015). Variants near CCK receptors are associated with electrophysiological responses to prepulse startle stimuli in a Mexican American cohort. Twin Research and Human Genetics : The Official Journal of the International Society for Twin Studies, 18(6), 727–737. http://doi.org/10.1017/thg.2015.77