RGD Reference Report - Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. - Rat Genome Database

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Habenular α5 nicotinic receptor subunit signalling controls nicotine intake.

Authors: Fowler, Christie D  Lu, Qun  Johnson, Paul M  Marks, Michael J  Kenny, Paul J 
Citation: Fowler CD, etal., Nature. 2011 Mar 31;471(7340):597-601. doi: 10.1038/nature09797. Epub 2011 Jan 30.
RGD ID: 150527840
Pubmed: PMID:21278726   (View Abstract at PubMed)
PMCID: PMC3079537   (View Article at PubMed Central)
DOI: DOI:10.1038/nature09797   (Journal Full-text)

Genetic variation in CHRNA5, the gene encoding the α5 nicotinic acetylcholine receptor subunit, increases vulnerability to tobacco addiction and lung cancer, but the underlying mechanisms are unknown. Here we report markedly increased nicotine intake in mice with a null mutation in Chrna5. This effect was 'rescued' in knockout mice by re-expressing α5 subunits in the medial habenula (MHb), and recapitulated in rats through α5 subunit knockdown in MHb. Remarkably, α5 subunit knockdown in MHb did not alter the rewarding effects of nicotine but abolished the inhibitory effects of higher nicotine doses on brain reward systems. The MHb extends projections almost exclusively to the interpeduncular nucleus (IPN). We found diminished IPN activation in response to nicotine in α5 knockout mice. Further, disruption of IPN signalling increased nicotine intake in rats. Our findings indicate that nicotine activates the habenulo-interpeduncular pathway through α5-containing nAChRs, triggering an inhibitory motivational signal that acts to limit nicotine intake.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Chrna5Ratbehavioral response to nicotine  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Chrna5  (cholinergic receptor nicotinic alpha 5 subunit)


Additional Information