RGD Reference Report - Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co-morbid expression of innate anxiety and excessive alcohol intake. - Rat Genome Database

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Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co-morbid expression of innate anxiety and excessive alcohol intake.

Authors: Stopponi, Serena  Fotio, Yannick  Domi, Ana  Borruto, Anna Maria  Natividad, Luis  Roberto, Marisa  Ciccocioppo, Roberto  Cannella, Nazzareno 
Citation: Stopponi S, etal., Addict Biol. 2018 Nov;23(6):1223-1232. doi: 10.1111/adb.12573. Epub 2017 Oct 26.
RGD ID: 408361844
Pubmed: PMID:29071769   (View Abstract at PubMed)
PMCID: PMC6625509   (View Article at PubMed Central)
DOI: DOI:10.1111/adb.12573   (Journal Full-text)

Fatty acid amide hydrolase (FAAH) is an enzyme that prominently degrades the major endocannabinoid N-arachidonoylethanolamine (anandamide). Inhibition of this enzyme leads to increased anandamide levels in brain regions that modulate stress and anxiety. Recently, we found that genetically selected Marchigian Sardinian alcohol-preferring (msP) rats display hyperactive FAAH in amygdalar regions that was associated with increased stress sensitivity and a hyper-anxious phenotype. Our previous work has also demonstrated that msPs display an innate preference for and excessive consumption of alcohol, potentially reflecting a form of self-medication to gain relief from hyper-anxious states. Here, we expand on our previous work by microinjecting the selective FAAH inhibitor URB597 (vehicle, 0.03, 0.1 and 1.0 μg per rat) into the central amygdala (CeA) and basolateral amygdala in msP versus non-selected Wistar rats to evaluate the effects of localized FAAH inhibition on operant alcohol self-administration and restraint-induced anxiety using the elevated plus maze. Intra-CeA URB597 significantly reduced alcohol self-administration in msP but not in Wistar rats. Intra-basolateral amygdala URB597 also attenuated alcohol drinking in msPs, although the effect was less pronounced relative to CeA treatment. In contrast, control experiments administering URB597 into the ventral tegmental area produced no genotypic differences in drinking. We also found that URB597 treatment in the CeA significantly reduced the anxiogenic effects of restraint stress in msPs, although no effects were detected in Wistars. Dysregulation of FAAH regulated systems in the major output region of the amygdala may drive the propensity for co-morbid expression of anxiety and excessive alcohol use.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FAAHHumanalcohol use disorder treatmentISOFaah (Rattus norvegicus) RGD 
FaahRatalcohol use disorder treatmentIMP  RGD 
FaahMousealcohol use disorder treatmentISOFaah (Rattus norvegicus) RGD 
sPRatalcohol use disorder treatmentIAGP compared to Wistar strainRGD 
FAAHHumanstress-related disorder treatmentISOFaah (Rattus norvegicus) RGD 
FaahRatstress-related disorder treatmentIMP  RGD 
FaahMousestress-related disorder treatmentISOFaah (Rattus norvegicus) RGD 
sPRatstress-related disorder treatmentIAGP compared to Wistar strain, vehicle treated or unrestrained ratsRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FaahRatresponse to ethanol  IMP  RGD 
FaahRatresponse to immobilization stress  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FaahRatabnormal anxiety-related response treatmentIMP  RGD 
sPRatabnormal anxiety-related response  IAGP compared to Wistar strainRGD 
FaahRatalcohol preference treatmentIMP  RGD 
sPRatalcohol preference  IAGP compared to Wistar strainRGD 
Objects Annotated

Genes (Rattus norvegicus)
Faah  (fatty acid amide hydrolase)

Genes (Mus musculus)
Faah  (fatty acid amide hydrolase)

Genes (Homo sapiens)
FAAH  (fatty acid amide hydrolase)

Strains
sP  (Sardinian alcohol-preferring rats)


Additional Information