RGD Reference Report - Profound alteration in reward processing due to a human polymorphism in CHRNA5: a role in alcohol dependence and feeding behavior. - Rat Genome Database

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Profound alteration in reward processing due to a human polymorphism in CHRNA5: a role in alcohol dependence and feeding behavior.

Authors: Besson, Morgane  Forget, Benoît  Correia, Caroline  Blanco, Rodolphe  Maskos, Uwe 
Citation: Besson M, etal., Neuropsychopharmacology. 2019 Oct;44(11):1906-1916. doi: 10.1038/s41386-019-0462-0. Epub 2019 Jul 9.
RGD ID: 150530288
Pubmed: PMID:31288250   (View Abstract at PubMed)
PMCID: PMC6785024   (View Article at PubMed Central)
DOI: DOI:10.1038/s41386-019-0462-0   (Journal Full-text)

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Chrna5Rathigh preference for an addictive substance  IMP compared to wild typeRGD 
Chrna5em20(D398N)PasRathigh preference for an addictive substance  IMP compared to wild typeRGD 
LE-Chrna5em20(D398N)PasRathigh preference for an addictive substance  IMP compared to wild typeRGD 
Chrna5Ratincreased alcohol consumption  IMP compared to wild typeRGD 
Chrna5em20(D398N)PasRatincreased alcohol consumption  IMP compared to wild typeRGD 
LE-Chrna5em20(D398N)PasRatincreased alcohol consumption  IMP compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Chrna5  (cholinergic receptor nicotinic alpha 5 subunit)
Chrna5em20(D398N)Pas  (cholinergic receptor, nicotinic, alpha 5 (neuronal); ZFN induced mutant 20,Pas)

Strains
LE-Chrna5em20(D398N)Pas  (NA)

Objects referenced in this article
Strain LE-Chrna5em18Pas null Rattus norvegicus

Additional Information