Enhanced Sensitivity to Attenuation of Conditioned Reinstatement by the mGluR2/3 Agonist LY379268 and Increased Functional Activity of mGluR2/3 in Rats with a History of Ethanol Dependence
Open accessAbstract
Recent findings implicate group II metabotropic glutamate receptors (mGluR(2/3)) in the reinforcing and dependence-inducing actions of ethanol and identify these receptors as treatment targets for alcoholism. Here, we investigated the effects of mGLuR(2/3) activation on conditioned reinstatement in rats with different ethanol-dependence histories and examined dependence-associated changes in the functional activity of mGluR(2/3). Following ethanol self-administration training and conditioning procedures, rats were made ethanol dependent, using ethanol vapor inhalation, under three conditions: a single intoxication and withdrawal episode (SW), repeated cycles of intoxication and withdrawal (RW), or no intoxication (CTRL). At 1 week after removal from ethanol vapor, self-administration resumed until stable baseline performance was reached, followed by extinction of operant responding and reinstatement tests. Post-withdrawal self-administration was increased in the RW group, but all groups showed conditioned reinstatement. The mGluR(2/3) agonist LY379268 dose -dependently reduced reinstatement in all groups, but was more effective at low doses in the SW and RW groups. The highest dose of LY379268 tested reduced spontaneous locomotor activity and operant responding maintained by a non-drug reinforcer, without differences among groups. The heightened sensitivity to the effects of LY379268 in rats with an ethanol-dependence history was therefore specific to behavior motivated by ethanol-related stimuli. Both the SW and RW groups showed elevated [(35)S]GTPγS binding in the central nucleus of the amygdala (CeA) and bed nucleus of stria terminalis (BNST), relative to the CTRL group. The findings implicate changes in mGluR(2/3) functional activity as a factor in ethanol dependence and support treatment target potential of mGlu(2/3) receptors for craving and relapse prevention.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies established a causal role for reduced prefrontal metabotropic glutamate receptor 2 function in craving and relapse responses in preclinical models of alcohol dependence.
“Several studies established a causal role for reduced prefrontal metabotropic glutamate receptor 2 (mGluR2) function in craving and relapse responses in preclinical models of alcohol dependence [48–52].”
From Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial (2024) · cites this paper as [52]
The Results section (page unavailable) reports no significant difference in mGluR2/3 functional activity in the medial prefrontal cortex of ethanol-dependent versus control rats. It instead reports increased activity in the central amygdala and bed nucleus of the stria terminalis. Although the paper finds that an mGluR2/3 agonist reduces reinstatement of ethanol seeking, it does not establish a causal role for reduced prefrontal mGluR2 function. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 69 · Cited by 72
Research works printed but not linked: 1
- Sinha R (ed) (2000). Stress, craving, and relapse to drug use. National Institute on Drug Abuse (NIDA) Symposium: The Intersection of Stress, Drug Abuse, and Development. Bethesda, MD.
- Authors
- Kufahl, P. R., Martin-Fardon, R., & Weiss, F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Kufahl, Peter R
- ORCID
- Weiss, Friedbert
- Venue
- Neuropsychopharmacology
- Published
- 2011-08-31
- Volume
- 36
- Issue
- 13
- Pages
- 2762-2773
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3230501
- OpenAlex
- W1984835419
- Cited by
- 72
- References
- 69
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 1 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 9 · 2013: 8 · 2012: 5
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Strong
- National Institutes of Health (AA010531)
- National Institute on Alcohol Abuse and Alcoholism (R01AA010531, AA010531, R01AA018010, AA018010)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- group II metabotropic glutamate receptors, mGluR2/3, LY379268, ethanol dependence, alcohol craving, relapse prevention, ethanol self-administration, withdrawal, central amygdala, bed nucleus of the stria terminalis, receptor sensitivity
- MeSH terms
- Ethanol, Alcoholism, Amino Acids, Animals, Central Nervous System Depressants, Conditioning, Psychological, Male, Self Administration, Rats, Wistar, Receptors, Metabotropic Glutamate, Bridged Bicyclo Compounds, Heterocyclic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
