Human and laboratory rodent low response to alcohol: is better consilience possible?

paper Cited Public

Authors: Crabbe, John C; Bell, Richard L; Ehlers, Cindy L
Year: 2010
Journal: Addiction biology
PMID: 20148776
DOI: 10.1111/j.1369-1600.2009.00191.x
PMCID: PMC2853481

If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of 'low level of responses to alcohol' determined by observing post-drinking-related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low level of response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and the rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: (1) behavioral measures of subjective intoxication; (2) body sway; (3) endocrine responses; and (4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively valenced and/or positively valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather sparse and unsystematic. Therefore, we suggest that more effort is still needed to collect data using refined measures designed to be more directly comparable in humans and animals. Additionally, the genetically mediated mechanisms underlying this endophenotype need to be characterized further across species.

#	Section	Preview
60	Locomotor Activating, Autonomic and Central Electrophysiological Responses to Alcohol Predictive of Risk — Central electrophysiological effects	Electrophysiological responses to alcohol have also been examined to a limited extent in lines of…
61	Locomotor Activating, Autonomic and Central Electrophysiological Responses to Alcohol Predictive of Risk — Summary	Together, these human and rodent findings suggest a promising area of research that could provide…
62	LR during peri-adolescence versus adulthood	Adolescence appears to be a period during which both humans and animals display lower responses to…
63	LR during peri-adolescence versus adulthood	vocalizations (Brasser, Spear 2002), and (d) decreased seizure threshold [ (Acheson et al. 1999) but…
64	LR during peri-adolescence versus adulthood	Whether adolescent LR has any firm correspondence with the low LR link to AD outcomes is unknown. LR…
65	LR phenotype(s): problems and promises	A low LR to alcohol as defined by multiple objective and subjective measures has been successfully…
66	LR phenotype(s): problems and promises	In order to study the mechanisms underlying low LR it would be important to know whether a single…
67	LR phenotype(s): problems and promises	which aspects of LR might be predictive or have different mechanisms (Schuckit, Smith 1996;Schuckit,…
68	LR phenotype(s): problems and promises	Table 2 summarizes the material we have reviewed in this article. We surveyed data from rodents…
69	LR phenotype(s): problems and promises	that some physiological mechanisms that underlie LR (variously described) seen in some rodent…
70	LR phenotype(s): problems and promises	species. We nonetheless advocate the pursuit of more consilient phenotypes as an additional…

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In this knowledge base

Title	Year	PMID
A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder.	2016	26117308
Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults.	2016	25039301
Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings.	2016	26809998
Endophenotypes for Alcohol Use Disorder: An Update on the Field.	2015	26236574
Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study.	2014	24094754
Relationships between impulsivity and subjective response in an IV ethanol paradigm.	2014	24553574
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	2014	25045619
Animal models for medications development targeting alcohol abuse using selectively bred rat lines: neurobiological and pharmacological validity.	2012	22841890

External

Title	Authors	Journal	Year	Link
The Dopamine System in Mediating Alcohol Effects in Humans.	Beck A et al.	—	2025	→
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A multicomponent ethanol response battery across a cumulative dose ethanol challenge reveals diminished adolescent rat ethanol responsivity relative to adults.	Vetreno RP et al.	—	2023	→
Behavioral response bias and event-related brain potentials implicate elevated incentive salience attribution to alcohol cues in emerging adults with lower sensitivity to alcohol.	Cofresí RU et al.	—	2022	→
Behavioral Profiles of Adolescent Alcohol-Preferring/Non-preferring (P/NP) and High/Low Alcohol-Drinking (HAD/LAD) Rats Are Dependent on Line but Not Sex.	Lundberg S et al.	—	2021	→
Transfer of incentive salience from a first-order alcohol cue to a novel second-order alcohol cue among individuals at risk for alcohol use disorder: electrophysiological evidence.	Fleming KA et al.	—	2021	→
Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans.	Parker CC et al.	—	2020	→
Getting to the Heart of Low Sensitivity to Alcohol: Context Moderates Low Cardiovascular Response to Alcohol in Persons With a Family History of Alcohol Use Disorder.	Bates ME et al.	—	2020	→
Evidence for incentive salience sensitization as a pathway to alcohol use disorder.	Cofresí RU et al.	—	2019	→
Studying alcohol use disorder using Drosophila melanogaster in the era of 'Big Data'.	Engel GL et al.	—	2019	→
What Is Addiction? How Can Animal and Human Research Be Used to Advance Research, Diagnosis, and Treatment of Alcohol and Other Substance Use Disorders?	Bickel WK et al.	—	2019	→
Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory behaviors in rats.	Mandt BH et al.	—	2018	→
The Cerebellar GABA<sub>A</sub>R System as a Potential Target for Treating Alcohol Use Disorder.	Rossi DJ et al.	—	2018	→
A preclinical model for identifying rats at risk of alcohol use disorder.	Jadhav KS et al.	—	2017	→
A Review of Developmental Considerations in Human Laboratory Alcohol Research.	Hendershot CS et al.	—	2017	→
Craving and acute effects of alcohol in youths' daily lives: Associations with alcohol use disorder severity.	Treloar H et al.	—	2017	→
Subjective alcohol responses in a cross-sectional, field-based study of adolescents and young adults: Effects of age, drinking level, and dependence/consequences.	Treloar H et al.	—	2017	→
Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior.	Crews FT et al.	—	2016	→
A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction.	Bell RL et al.	—	2016	→
A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder.	King AC et al.	—	2016	→
Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults.	Hendershot CS et al.	—	2016	→
Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.	Al-Noori S et al.	—	2016	→
Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings.	Bell RL et al.	—	2016	→
Endophenotypes for Alcohol Use Disorder: An Update on the Field.	Salvatore JE et al.	—	2015	→
Predicting addictive vulnerability: individual differences in initial responding to a drug's pharmacological effects.	Ramsay DS et al.	—	2015	→
Quantitative trait locus mapping of acute functional tolerance in the LXS recombinant inbred strains.	Bennett B et al.	—	2015	→
Supplier-dependent differences in intermittent voluntary alcohol intake and response to naltrexone in Wistar rats.	Momeni S et al.	—	2015	→
XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans.	Juraeva D et al.	—	2015	→
Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study.	King AC et al.	—	2014	→
Relationships between impulsivity and subjective response in an IV ethanol paradigm.	Leeman RF et al.	—	2014	→
The Genetics, Neurogenetics and Pharmacogenetics of Addiction.	Demers CH et al.	—	2014	→
Genetic studies of acute tolerance, rapid tolerance, and drinking in the dark in the LXS recombinant inbred strains.	Radcliffe RA et al.	—	2013	→
Individual predictors of the subjective effects of intravenous cocaine.	Grasing K et al.	—	2013	→
Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.	Blednov YA et al.	—	2013	→
Modeling the diagnostic criteria for alcohol dependence with genetic animal models.	Crabbe JC et al.	—	2013	→
Sensitivity to reinforcer delay predicts ethanol's suppressant effects, but itself is unaffected by ethanol.	Moschak TM et al.	—	2013	→
The β2 nicotinic acetylcholine receptor subunit differentially influences ethanol behavioral effects in the mouse.	Dawson A et al.	—	2013	→
Animal models for medications development targeting alcohol abuse using selectively bred rat lines: neurobiological and pharmacological validity.	Bell RL et al.	—	2012	→
Bridging Animal and Human Models: Translating From (and to) Animal Genetics.	Barkley-Levenson AM et al.	—	2012	→
Dependence induced increases in intragastric alcohol consumption in mice.	Fidler TL et al.	—	2012	→
Discovering genes involved in alcohol dependence and other alcohol responses: role of animal models.	Buck KJ et al.	—	2012	→
Ethanol sensitivity in high drinking in the dark selectively bred mice.	Crabbe JC et al.	—	2012	→
Ethanol tolerance and withdrawal severity in high drinking in the dark selectively bred mice.	Crabbe JC et al.	—	2012	→
Impaired control over alcohol use: An under-addressed risk factor for problem drinking in young adults?	Leeman RF et al.	—	2012	→
Introduction to the special issue "Pharmacotherapies for the treatment of alcohol abuse and dependence" and a summary of patents targeting other neurotransmitter systems.	Bell RL et al.	—	2012	→
Medications development to treat alcohol dependence: a vision for the next decade.	Litten RZ et al.	—	2012	→
Oral Nicotine Self-Administration in Rodents.	Collins AC et al.	—	2012	→
Translational behaviour-genetic studies of alcohol: are we there yet?	Crabbe JC	—	2012	→
Identifying neurobiological phenotypes associated with alcohol use disorder severity.	Claus ED et al.	—	2011	→
Molecular targets of alcohol action: Translational research for pharmacotherapy development and screening.	Gorini G et al.	—	2011	→
Publication trends in addiction research.	Helinski S et al.	—	2011	→
The genetic relationships between ethanol preference, acute ethanol sensitivity, and ethanol tolerance in Drosophila melanogaster.	Devineni AV et al.	—	2011	→