The complexity of alcohol drinking: studies in rodent genetic models.
paper
Cited
Public
- Authors
- Crabbe, John C; Phillips, Tamara J; Belknap, John K
- Year
- 2010
- Journal
- Behavior genetics
- PMID
- 20552264
- DOI
- 10.1007/s10519-010-9371-z
- PMCID
- PMC3330823
Risk for alcohol dependence in humans has substantial genetic contributions. Successful rodent models generally attempt to address only selected features of the human diagnosis. Most such models target the phenotype of oral administration of alcohol solutions, usually consumption of or preference for an alcohol solution versus water. Data from rats and mice for more than 50 years have shown genetic influences on preference drinking and related phenotypes. This paper summarizes some key findings from that extensive literature. Much has been learned, including the genomic location and possible identity of several genes influencing preference drinking. We report new information from congenic lines confirming QTLs for drinking on mouse chromosomes 2 and 9. There are many strengths of the various phenotypic assays used to study drinking, but there are also some weaknesses. One major weakness, the lack of drinking excessively enough to become intoxicated, has recently been addressed with a new genetic animal model, mouse lines selectively bred for their high and intoxicating blood alcohol levels after a limited period of drinking in the circadian dark. We report here results from a second replicate of that selection and compare them with the first replicate.
Introgression of a genetic DBA/2J (D2) strain segment onto a pure C57BL/6J strain background reduces ethanol consumption. Shown is mean SEM consumption of 10% ethanol in Chromosome 2 (left) or Chromosome 9 (right) congenic and background strain mice. Introgression of a B6 segment on the alcohol avoiding D2 background did not significantly alter ethanol consumption. Congenic interval: B6.D2 Chromosome 2: 10โ86 cM; D2.B6 Chromosome 2: 37โ71 cM; both B6.D2 and D2.B6 Chromosome 9: 9โ58 cM. *** p < 0.01 for the comparison of B6 to B6.D2 congenic mice
Realized response to selection for high blood ethanol concentration (BEC) in High Drinking in the Dark (HDID-1 and HDID-2) mice. Response is shown across 13 selected generations for HDID-1 mice and 7 generations for HDID-2 mice. Mean ยฑ SEM BEC is shown. Circles represent the total population tested each generation. Inverted triangles give values of the animals chosen as parents from the preceding generation: their offspring are represented in circles directly below. For a detailed discussion of the first 11 generations of the HDID-1 selection, as well as the specific methods used, see (Crabbe et al. 2009)
Increased consumption in the HDID-1 and HDID-2 selected lines across generations. Mean ยฑ SEM g kg ethanol ingested during the second day of DID testing is shown. Intake is a correlated response to selection on the BEC levels depicted in Fig. 2. In HDID-1 mice, as BEC tripled across the first 11 generations, intake increased by 50%
| # | Section | Preview |
|---|---|---|
| 40 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Selection for high blood ethanol concentrations | To provide a new model of binge-like drinking, we bred a mouse line for high blood ethanol levelsโฆ |
| 41 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Selection for high blood ethanol concentrations | offered water, the HDID-1 mice were shown to be intoxicated in the balance beam test. Theโฆ |
| 42 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Selection for high blood ethanol concentrations | To provide a replicate that could be used to verify any correlated responses to selection, weโฆ |
| 43 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Selection for high blood ethanol concentrations | BEC and not on intake, the intakes have increased as a genetically correlated response to selectionโฆ |
| 44 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Selection for high blood ethanol concentrations | After 9 generations of selection for high DID, the HDID-1 mice were tested in a standard DID test,โฆ |
| 45 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Pharmacological modulation of drinking in the dark | The DID paradigm has been used in several laboratories to explore pharmacological control of thisโฆ |
| 46 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Pharmacological modulation of drinking in the dark | the GABA-A agonists muscimol and THIP reduced ethanol intake, but also water (Moore et al. 2007).โฆ |
| 47 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Pharmacological modulation of drinking in the dark | of double-labeled cells in the ventral tegmental area while nicotine pretreatment did notโฆ |
| 48 | Beyond alcohol preference drinking โ Drinking in the Darkโa new genetic animal model โ Pharmacological modulation of drinking in the dark | We are aware of only three studies to date that have employed a modification of the DID model toโฆ |
| 49 | Future directions | The tendency of some rodents to prefer and others to avoid alcohol solutions has provided theโฆ |
| 50 | Future directions | outset. In part, this is because alcoholism is a developmental, chronically relapsing disorder, andโฆ |
| 51 | Future directions | Several investigators recently made an effort to review the state of the art in human and animalโฆ |
| 52 | Future directions | to circadian time, and across drinking sessions. Finally, the need for measuring BECs in all studiesโฆ |
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| Title | Year | PMID |
|---|---|---|
| Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study. | 2014 | 24094754 |
| Genetic research: who is at risk for alcoholism. | 2010 | 23579937 |
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Animal Models of Excessive Alcohol Consumption in Rodents. | Becker HC et al. | โ | 2025 | โ |
| Epigenetic Dysregulation in Alcohol-Associated Behaviors: Preclinical and Clinical Evidence. | Domi E et al. | โ | 2025 | โ |
| Modeling Brain Gene Expression in Alcohol Use Disorder with Genetic Animal Models. | Hitzemann R et al. | โ | 2025 | โ |
| Chronic alcohol consumption shifts learning strategies and synaptic plasticity from hippocampus to striatum-dependent pathways. | Tochon L et al. | โ | 2023 | โ |
| Network States in the Basolateral Amygdala Predicts Voluntary Alcohol Consumption | DiLeo A et al. | โ | 2023 | โ |
| From binge eating to binge drinking: A new and robust paradigm for assessing binge ethanol self-administration in male rats. | Ruiz-Leyva L et al. | โ | 2022 | โ |
| Increased Voluntary Alcohol Consumption in Mice Lacking GABA<sub>B(1)</sub> Is Associated With Functional Changes in Hippocampal GABA<sub>A</sub> Receptors. | Floris G et al. | โ | 2022 | โ |
| Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways. | Mineur YS et al. | โ | 2022 | โ |
| Effects of vapourized THC and voluntary alcohol drinking during adolescence on cognition, reward, and anxiety-like behaviours in rats. | Hamidullah S et al. | โ | 2021 | โ |
| Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation? | Borruto AM et al. | โ | 2021 | โ |
| On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption. | Hitzemann R et al. | โ | 2021 | โ |
| Photic Regulation of Circadian Rhythms and Voluntary Ethanol Intake: Role of Melanopsin-expressing Intrinsically Photosensitive Retinal Ganglion Cells. | Hartmann MC et al. | โ | 2021 | โ |
| Reduction of Cell Proliferation by Acute C<sub>2</sub>H<sub>6</sub>O Exposure. | Baldari S et al. | โ | 2021 | โ |
| The impact of Drinking in the Dark (DID) procedural manipulations on ethanol intake in High Drinking in the Dark (HDID) mice. | Savarese AM et al. | โ | 2021 | โ |
| Allosteric modulation of metabotropic glutamate receptors in alcohol use disorder: Insights from preclinical investigations. | Johnson KA et al. | โ | 2020 | โ |
| Investigating Alcohol Behavior and Physiology Using Drosophila melanogaster. | De Nobrega AK et al. | โ | 2020 | โ |
| Low-dose ethanol intake prevents high-fat diet-induced adverse cardiovascular events in mice. | Nie J et al. | โ | 2020 | โ |
| Pre-clinical models of reward deficiency syndrome: A behavioral octopus. | Gondrรฉ-Lewis MC et al. | โ | 2020 | โ |
| Voluntary alcohol consumption is increased in female, but not male, oxytocin receptor knockout mice. | Rodriguez KM et al. | โ | 2020 | โ |
| Convergent Evidence From Humans and Drosophila melanogaster Implicates the Transcription Factor MEF2B/Mef2 in Alcohol Sensitivity. | Schmitt RE et al. | โ | 2019 | โ |
| Environmental Enrichment During Adulthood Reduces Sucrose Binge-Like Intake in a High Drinking in the Dark Phenotype (HD) in C57BL/6J Mice. | Rodrรญguez-Ortega E et al. | โ | 2019 | โ |
| Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement. | Morel C et al. | โ | 2019 | โ |
| Rigor and reproducibility in rodent behavioral research. | Gulinello M et al. | โ | 2019 | โ |
| Studying alcohol use disorder using Drosophila melanogaster in the era of 'Big Data'. | Engel GL et al. | โ | 2019 | โ |
| Behavioral Evaluation of Seeking and Preference of Alcohol in Mice Subjected to Stress. | Canseco-Alba A et al. | โ | 2018 | โ |
| Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory behaviors in rats. | Mandt BH et al. | โ | 2018 | โ |
| The role of the orbitofrontal cortex in alcohol use, abuse, and dependence. | Moorman DE | โ | 2018 | โ |
| Animal models of addiction. | Spanagel R | โ | 2017 | โ |
| Genetic correlation between alcohol preference and conditioned fear: Exploring a functional relationship. | Chester JA et al. | โ | 2017 | โ |
| Rat animal models for screening medications to treat alcohol use disorders. | Bell RL et al. | โ | 2017 | โ |
| Tobacco and alcohol use during adolescence: Interactive mechanisms in animal models. | Abreu-Villaรงa Y et al. | โ | 2017 | โ |
| Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort. | Lopez MF et al. | โ | 2017 | โ |
| Common genes regulate food and ethanol intake in Drosophila. | Sekhon ML et al. | โ | 2016 | โ |
| The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction. | Casartelli L et al. | โ | 2016 | โ |
| Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling. | Darlington TM et al. | โ | 2016 | โ |
| ฮฒ-endorphin regulates alcohol consumption induced by exercise restriction in female mice. | McGonigle CE et al. | โ | 2016 | โ |
| Alcohol-Preferring Rats Show Goal Oriented Behaviour to Food Incentives but Are Neither Sign-Trackers Nor Impulsive. | Peรฑa-Oliver Y et al. | โ | 2015 | โ |
| Influence of sex on genetic regulation of "drinking in the dark" alcohol consumption. | Vanderlinden LA et al. | โ | 2015 | โ |
| N-methyl-D-aspartate receptor antagonism has differential effects on alcohol craving and drinking in heavy drinkers. | Krishnan-Sarin S et al. | โ | 2015 | โ |
| Quantification of alcohol drinking patterns in mice. | Eisenhardt M et al. | โ | 2015 | โ |
| Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study. | King AC et al. | โ | 2014 | โ |
| A model of alcohol drinking under an intermittent access schedule using group-housed mice. | Smutek M et al. | โ | 2014 | โ |
| Animal models of excessive alcohol consumption: recent advances and future challenges. | Becker HC et al. | โ | 2014 | โ |
| Behavioral disinhibition in mice bred for high drinking in the dark (HDID) and HS controls increases following ethanol. | Tipps ME et al. | โ | 2014 | โ |
| Effects of stress, acute alcohol treatment, or both on pre-pulse inhibition in high- and low-alcohol preferring mice. | Powers MS et al. | โ | 2014 | โ |
| High drinking in the dark mice: a genetic model of drinking to intoxication. | Barkley-Levenson AM et al. | โ | 2014 | โ |
| Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice. | Crabbe JC et al. | โ | 2014 | โ |
| Proteomic approaches and identification of novel therapeutic targets for alcoholism. | Gorini G et al. | โ | 2014 | โ |
| Recent advances with a novel model organism: alcohol tolerance and sensitization in zebrafish (Danio rerio). | Tran S et al. | โ | 2014 | โ |
| Relation between corticosterone and fear-related behavior in mice selectively bred for high or low alcohol preference. | Chester JA et al. | โ | 2014 | โ |
| Rodent models of genetic contributions to motivation to abuse alcohol. | Crabbe JC | โ | 2014 | โ |
| Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access. | Matson LM et al. | โ | 2014 | โ |
| Use of animal models of alcohol-related behavior. | Crabbe JC | โ | 2014 | โ |
| Advanced transgenic approaches to understand alcohol-related phenotypes in animals. | Bilbao A | โ | 2013 | โ |
| A multistep general theory of transition to addiction. | Piazza PV et al. | โ | 2013 | โ |
| Animal models of alcohol and drug dependence. | Planeta CS | โ | 2013 | โ |
| Caffeinated Alcoholic Beverages - An Emerging Trend in Alcohol Abuse. | Franklin KM et al. | โ | 2013 | โ |
| Convergent functional genomics in addiction research - a translational approach to study candidate genes and gene networks. | Spanagel R | โ | 2013 | โ |
| Effects of intoxicating free-choice alcohol consumption during adolescence on drinking and impulsivity during adulthood in selectively bred high-alcohol preferring mice. | O'Tousa DS et al. | โ | 2013 | โ |
| Escalation of intake under intermittent ethanol access in diverse mouse genotypes. | Rosenwasser AM et al. | โ | 2013 | โ |
| Genetic studies of acute tolerance, rapid tolerance, and drinking in the dark in the LXS recombinant inbred strains. | Radcliffe RA et al. | โ | 2013 | โ |
| "Jelloยฎ shots" and cocktails as ethanol vehicles: parametric studies with high- and low-saccharin-consuming rats. | Dess NK et al. | โ | 2013 | โ |
| Modeling the diagnostic criteria for alcohol dependence with genetic animal models. | Crabbe JC et al. | โ | 2013 | โ |
| Pharmacologically relevant intake during chronic, free-choice drinking rhythms in selectively bred high alcohol-preferring mice. | Matson LM et al. | โ | 2013 | โ |
| Selective breeding for ethanol-related traits alters circadian phenotype. | McCulley WD et al. | โ | 2013 | โ |
| Addictive drugs and plasticity of glutamatergic synapses on dopaminergic neurons: what have we learned from genetic mouse models? | Rodriguez Parkitna J et al. | โ | 2012 | โ |
| Do initial responses to drugs predict future use or abuse? | de Wit H et al. | โ | 2012 | โ |
| Effects of cross-fostering on alcohol preference and correlated responses to selection in high- and low-alcohol-preferring mice. | Barrenha GD et al. | โ | 2012 | โ |
| Ethanol sensitivity in high drinking in the dark selectively bred mice. | Crabbe JC et al. | โ | 2012 | โ |
| Ethanol tolerance and withdrawal severity in high drinking in the dark selectively bred mice. | Crabbe JC et al. | โ | 2012 | โ |
| Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions. | Crabbe JC et al. | โ | 2012 | โ |
| Intermittent availability of ethanol does not always lead to elevated drinking in mice. | Crabbe JC et al. | โ | 2012 | โ |
| Neurochemical and neurostructural plasticity in alcoholism. | Gass JT et al. | โ | 2012 | โ |
| Translational behaviour-genetic studies of alcohol: are we there yet? | Crabbe JC | โ | 2012 | โ |
| Alcohol preference drinking in a mouse line selectively bred for high drinking in the dark. | Crabbe JC et al. | โ | 2011 | โ |
| A systems genetic analysis of alcohol drinking by mice, rats and men: influence of brain GABAergic transmission. | Saba LM et al. | โ | 2011 | โ |
| Intragastric self-infusion of ethanol in high- and low-drinking mouse genotypes after passive ethanol exposure. | Fidler TL et al. | โ | 2011 | โ |
| Molecular targets of alcohol action: Translational research for pharmacotherapy development and screening. | Gorini G et al. | โ | 2011 | โ |
| Preclinical studies of alcohol binge drinking. | Crabbe JC et al. | โ | 2011 | โ |
| Protein database and quantitative analysis considerations when integrating genetics and proteomics to compare mouse strains. | Fei SS et al. | โ | 2011 | โ |
| Subjective responses to alcohol: a paradigm shift may be brewing. | King AC et al. | โ | 2011 | โ |
| Genetic research: who is at risk for alcoholism. | Foroud T et al. | โ | 2010 | โ |