Wilhelm CJ, Mitchell SH. Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes. Genes Brain Behav 7: 705-713

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Genes Brain and Behavior (Impact Factor: 3.66). 10/2008; 7(7):705-13. DOI: 10.1111/j.1601-183X.2008.00406.x
Source: PubMed


Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.

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    • "For example, negative and positive urgency are impulsivity traits defined as the tendency to act rashly while in heightened emotional states[10,11]. Negative urgency, a heightened negative emotional state, in particular is significantly correlated with severe anxiety symptoms and is a strong predictor of alcoholism[10,12,13]. Similar to human alcoholics and heavy drinkers47484950, HAD- 1 rats score significantly higher on measures of impulsivity and risk-taking than their low alcohol drinking (LAD-1) counterparts[51]. In addition, our current findings show that HAD-1 rats possess a unique emotional phenotype comprised of an unusually high proportion of negative affect USVs that is further enhanced by alcohol consumption. "

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    • "For this study, in addition to lesioning the dopaminergic neurons by progressive administration of MPTP, cognitive deficits are behaviorally analyzed by a cued response task that requires animals to learn a stimulus–action–outcome contingency as well as to acquire the ability to exhibit behavioral flexibility, depending on the stimulus present at a given time (Wilhelm and Mitchell, 2008). This study examines behavioral changes via simple executive function testing and their relationships to dopaminergic and glutamatergic protein expression in the dorsolateral (DL) striatum, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in a progressive MPTP mouse model. "
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    ABSTRACT: Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine-1 receptor and vesicular glutamate transporter (VGLUT)-1 expression increased in the mPFC following DA loss. There were significant MPTP-induced decreases and increases in VGLUT-1 and VGLUT-2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical-cortical (VGLUT-1) glutamate function but also in striatal DA and glutamate (VGLUT-1/VGLUT-2) input. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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    • ", in a direction similar to that reported by Poulos et al . ; Beckwith & Czachowski , 2014 ; Oberlin & Grahame , 2009 ; Wilhelm & Mitchell , 2008 ) , some demonstrates no relation ( Beckwith & Czachowski ) , or the opposite relation ( Wilhelm , Reeves , Phillips , & Mitchell , 2007 ) between these variables . These inconsistencies diminish the utility of examining alcohol consumption in rodent models when attempting to under - stand the relation between experimental manipulation of impulsive choice and subse - quent drug self - administration . "
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    ABSTRACT: In a prior study (Stein et al., 2013), we reported that rats pre-exposed to delayed rewards made fewer impulsive choices, but consumed more alcohol (12% wt/vol), than rats pre-exposed to immediate rewards. To understand the mechanisms that produced these findings, we again pre-exposed rats to either delayed (17.5 s; n = 32) or immediate (n = 30) rewards. In posttests, delay-exposed rats made significantly fewer impulsive choices at 15- and 30-s delays to a larger, later food reward than the immediacy-exposed comparison group. Behavior in an open-field test provided little evidence of differential stress exposure between groups. Further, consumption of either 12% alcohol or isocaloric sucrose in subsequent tests did not differ between groups. Because Stein et al. introduced alcohol concentration gradually (3-12%), we speculate that their group differences in 12% alcohol consumption were not determined by alcohol's pharmacological effects, but by another variable (e.g., taste) that was preserved as an artifact from lower concentrations. We conclude that pre-exposure to delayed rewards generalizes beyond the pre-exposure delay; however, this same experimental variable does not robustly influence alcohol consumption. © Society for the Experimental Analysis of Behavior.
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