Activation of Brain NOP Receptors Attenuates Acute and Protracted Alcohol Withdrawal Symptoms in the Rat: N/OFQ REDUCES ALCOHOL WITHDRAWAL SYMPTOMS IN RATS
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BACKGROUND: Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS: For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). RESULTS: Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS: These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms.
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Neuropeptide Y, nociceptin, and endocannabinoids act in opposition to brain stress systems.
“Key neurotransmitters that act in opposition to brain stress systems include neuropeptide Y, nociceptin, and endocannabinoids (tables 1, 2, circuits 10 and 11).”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [28]
The Introduction (page not provided) says nociceptin/orphanin FQ has anti-stress effects and acts as a functional antagonist of CRF transmission. The cited paper does not establish the same claim for neuropeptide Y or endocannabinoids. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFor alcohol, intracerebroventricular nociceptin administration significantly reduces expression of somatic withdrawal signs and reverses anxiety-like behaviors associated with both chronic and acute alcohol intoxication in Wistar rats.
“For alcohol, intracerebroventricular nociceptin administration significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors that were associated with both chronic and acute alcohol intoxication in Wistar rats (Economidou et al., 2011).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Economidou et al., 2011
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- Authors
- Economidou, D., Cippitelli, A., Stopponi, S., Braconi, S., Clementi, S., Ubaldi, M., Martin-Fardon, R., Weiss, F., Massi, M., & Ciccocioppo, R.
- Affiliations
- Università di Camerino (IT)
- Corresponding author
- Ciccocioppo, Roberto
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2011-01-11
- Volume
- 35
- Issue
- 4
- Pages
- 747-755
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC3066303
- OpenAlex
- W1927728226
- Semantic Scholar
- 934d8cd9015ac15f6ea08c54ba0cd9346b003043
- Cited by
- 71
- References
- 65
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 3 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 5
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA014351, R01AA014351)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Alcoholism and Thiamine Deficiency
- Keywords
- nociceptin/orphanin FQ, NOP receptor, alcohol withdrawal, chronic alcohol intoxication, anxiety-like behavior, somatic withdrawal signs, intracerebroventricular administration, alcoholism treatment
- MeSH terms
- Nociceptin Receptor, Ethanol, Alcoholism, Animals, Anxiety, Brain, Central Nervous System Depressants, Disease Models, Animal, Male, Peptide Fragments, Receptors, Opioid, Substance Withdrawal Syndrome, Time Factors, Rats, Wistar, Neurotransmitter Agents, Maze Learning, Opioid Peptides, Rats
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