Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co-morbid expression of innate anxiety and excessive alcohol intake
Open accessAbstract
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.
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Self-citation
- Authors
- Stopponi, S., Fotio, Y., Domi, A., Borruto, A. M., Natividad, L., Roberto, M., Ciccocioppo, R., & Cannella, N.
- Affiliations
- Università di Camerino (IT)
- Scripps Research Institute (US)
- Corresponding author
- Ciccocioppo, Roberto
- ORCID
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2017-10-26
- Volume
- 23
- Issue
- 6
- Pages
- 1223-1232
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC6625509
- OpenAlex
- W2765649731
- Cited by
- 48
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 4
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- Funders
- NIH NIAAA (AA017447)
- the National Institute on Alcohol Abuse and Alcoholism (R01-AA015566, R37-AA017447)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- fatty acid amide hydrolase, FAAH inhibition, URB597, anandamide, endocannabinoid system, central amygdala, basolateral amygdala, alcohol self-administration, anxiety, restraint stress, alcoholism, self-medication
- MeSH terms
- Fatty Acid Amide Hydrolases, Ethanol, Alcoholism, Amidohydrolases, Analysis of Variance, Animals, Anxiety Disorders, Benzamides, Carbamates, Central Nervous System Depressants, Conditioning, Operant, Enzyme Inhibitors, Male, Microinjections, Rats, Inbred Strains, Restraint, Physical, Self Administration, Stress, Psychological, Rats, Wistar, Maze Learning, Central Amygdaloid Nucleus
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