Excessive alcohol ingestion, occasionally or chronically, is co-morbid with medical disorders affecting the brain and behavior as well as other organ damage. Much of what is known about risk for and the consequence of heavy alcohol consumption, including mechanisms of organ damage, is derived from rodent studies or retrospective human accounts. This application proposes establishing a unique resource for alcohol research, a Monkey Alcohol Tissue Research Resource (MATRR). From this resource both tissue and associated bioinformatics tools will be made readily available to the wider alcohol research community. The tissue is derived from a standard protocol of ethanol self-administration in 3 species of monkeys. This resource will provide novel data for hypothesis testing relating the risk for and consequences of alcohol consumption and serve to bi-directionally bridge the gap between rodent and human studies. The basis of the MATRR is that non human primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent/day) over long periods of time (12-30 months) with concomitant pathological changes in endocrine, hepatic and central nervous system (CNS) processes. These longitudinal designs span """"""""stages of drinking"""""""" from ethanol-nai've to early alcohol exposure to chronic abuse. The CNS and peripheral organs from these animals comprise a unique translational resource for mechanistic and genetic studies of ethanol-induced pathologies. The state-of-the-art necropsy protocol will provide fresh, fixed and frozen tissue that are appropriate for ex vivo electrophysiology and neurochemical recordings, histological studies and genomic, proteomic and metabolomic approaches, respectively. The demand for, and the quality of, the tissues are already high as reflected in the number of requests and publications. Nevertheless, this resource needs further development in order to fulfill its potential as a cutting edge translational tool in alcoholism research. Thus, the primary goal of this proposal is to build the resources of this tissue bank and distribute these tissues and/or associated bioinformatics, to the broader alcohol research community.
The research outlined in this proposal will establish a unique post-mortem tissue bank for alcohol research. Using sophisticated techniques tissues from populations of monkeys that have been chronically drinking alcohol and the related drinking and genetic information will be disseminated to the wider alcohol research community to better understand disease processes associated with alcoholism.
|Baker, Erich J; Walter, Nicole A R; Salo, Alex et al. (2017) Identifying Future Drinkers: Behavioral Analysis of Monkeys Initiating Drinking to Intoxication is Predictive of Future Drinking Classification. Alcohol Clin Exp Res 41:626-636|
|Nimitvilai, Sudarat; Uys, Joachim D; Woodward, John J et al. (2017) Orbitofrontal Neuroadaptations and Cross-Species Synaptic Biomarkers in Heavy-Drinking Macaques. J Neurosci 37:3646-3660|
|Shnitko, Tatiana A; Allen, Daicia C; Gonzales, Steven W et al. (2017) Ranking Cognitive Flexibility in a Group Setting of Rhesus Monkeys with a Set-Shifting Procedure. Front Behav Neurosci 11:55|
|Cervera-Juanes, Rita; Wilhelm, Larry J; Park, Byung et al. (2017) Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking. Alcohol 60:103-113|
|Cuzon Carlson, Verginia C; Grant, Kathleen A; Lovinger, David M (2017) Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset. Neuropharmacology 131:128-142|
|Akinyeke, Tunde; Weber, Sydney J; Davenport, April T et al. (2017) Effects of alcohol on c-Myc protein in the brain. Behav Brain Res 320:356-364|
|Beattie, Matthew C; Maldonado-Devincci, Antoniette M; Porcu, Patrizia et al. (2017) Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3?,5?)3-hydroxypregnan-20-one (3?,5?-THP) in the amygdala of the cynomolgus monkey. Addict Biol 22:318-330|
|Jimenez, Vanessa A; Allen, Daicia C; McClintick, Megan N et al. (2017) Social setting, social rank and HPA axis response in cynomolgus monkeys. Psychopharmacology (Berl) 234:1881-1889|
|Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Alberto, Greg E et al. (2017) Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals. Drug Alcohol Depend 177:244-248|
|Cervera-Juanes, R; Wilhelm, L J; Park, B et al. (2017) Alcohol-dose-dependent DNA methylation and expression in the nucleus accumbens identifies coordinated regulation of synaptic genes. Transl Psychiatry 7:e994|
Showing the most recent 10 out of 53 publications