Evidence map›Paper›PMID 29071769›Full record

ArticleAddiction biology2018

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

Serena Stopponi, Yannick Fotio, Ana Domi, Anna Maria Borruto, Luis Natividad, Marisa Roberto, Roberto Ciccocioppo, Nazzareno Cannella

Open access · greenAbstract read
In one paragraph

Article in Addiction biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
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  4. Observational
  5. FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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  14. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Serena StopponiSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Yannick FotioSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Ana DomiSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Anna Maria BorrutoSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Luis NatividadDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-9837-4670
Marisa RobertoDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-0729-3961
Roberto CiccocioppoSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.ORCID 0000-0003-3126-9240
Nazzareno CannellaSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Università di Camerino · ITScripps Research Institute · US

Funding

Regulation of Ethanol Effects on Synaptic TransmissionR01AA015566 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2006 to 2019
$4.6M
Gene-environment interaction: the brain CRF system in alcohol preferring msP ratsR37AA017447 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2016 to 2025
$3.7M
Identification of novel mechanisms in alcohol-induced cognitive dysfunctionK99AA025393 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI NATIVIDAD, LUIS ALBERTO · 2017 to 2018
$284k
NIAAA NIH HHS K99 AA025393NIAAA NIH HHS R01 AA015566NIAAA NIH HHS R37 AA017447
6 · The paper itself

Abstract

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.

Indexed as

AlcoholismAmidohydrolasesAnalysis of VarianceAnimalsAnxiety DisordersBenzamidesCarbamatesCentral Amygdaloid NucleusCentral Nervous System DepressantsConditioning, OperantEnzyme InhibitorsEthanolFatty Acid Amide HydrolasesMaleMaze LearningMicroinjectionsAmidohydrolasesBenzamidesCarbamatesCentral Nervous System Depressantscyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl esterEnzyme InhibitorsEthanolFatty Acid Amide Hydrolasesabuseaddictionalcoholismethanolstress

Identifiers

PMID29071769
PMCPMC6625509
OpenAlexW2765649731

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.