Human alcohol research and clinical practice demonstrate that, without question, there is a wide range of individual variation in risk for excessive drinking, in sensitivity to alcohol effects, and in response to treatment strategies. Impulsive behaviors are recognized as one risk factor, particularly if the construct of impulsive behaviors encompasses measures of both response inhibition and temporal discounting. A history of heavy ethanol intake appears to be related to increases in these measures of impulsivity. However human studies have been unable to distinguish antecedent baseline measures of impulsivity from the consequential effects of a history of heavy ethanol consumption. Our model of ethanol self-administration in cynomolgus monkeys provides a unique and important model of alcohol abuse, and reflects the individual differences in propensity to drink alcohol noted in the human population. Because of genetic similarities between humans and nonhuman primates, these studies can then be a key step in translating candidate mechanisms of ethanol's effects into the human condition through functional genomics. Thus, our primary focus of this PARC project is to use the monkey model to characterize antecedent and consequent measures of two aspects of impulsivity (response inhibition and aversion to a delay in reinforcement) with genetic factors related to excessive ethanol self-administration.
This project addresses a fundamental goal of the Portland Alcohol Research Center, namely the intersection of individual risk for heavy alcohol consumption with genetic mechanisms in prefrontal cortical regions correlated with measures of impulsivity. Macaque monkeys are proposed to address this goal because of their similarity to human beings in their genetics and neurobiology and the ability to conduct long-term longitudinal studies related to the risk for and/or consequence of excessive ethanol self-administration.
|Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C (2016) Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity. Physiol Behav 165:257-66|
|Shi, Xiao; Walter, Nicole A R; Harkness, John H et al. (2016) Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function. PLoS One 11:e0152581|
|Smith, Monique L; Hostetler, Caroline M; Heinricher, Mary M et al. (2016) Social transfer of pain in mice. Sci Adv 2:e1600855|
|Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly D2 receptors in nucleus accumbens core. Drug Alcohol Depend 158:159-63|
|Barkley-Levenson, Amanda M; Ryabinin, Andrey E; Crabbe, John C (2016) Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication. Behav Brain Res 302:160-70|
|Shabani, Shkelzen; Houlton, Sydney K; Hellmuth, Laura et al. (2016) A Mouse Model for Binge-Level Methamphetamine Use. Front Neurosci 10:493|
|Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P et al. (2016) Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection. G3 (Bethesda) 6:3893-3902|
|Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology (Berl) 233:1435-43|
|Crabbe, John C; Schlumbohm, Jason P; Hack, Wyatt et al. (2016) Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking. Alcohol 52:25-32|
|Smith, M L; Li, J; Cote, D M et al. (2016) Effects of isoflurane and ethanol administration on c-Fos immunoreactivity in mice. Neuroscience 316:337-43|
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