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Cited by 112Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

The Role of the Central Amygdala in Alcohol Dependence

Open access
Roberto, Marisa, Kirson, Dean, Khom, Sophia·2021·Cold Spring Harbor Perspectives in Medicine
DOI 10.1101/cshperspect.a039339PMC PMC7382982
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Abstract

Alcohol dependence is a chronically relapsing disorder characterized by compulsive drugseeking and drug-taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug.Accumulating evidence suggests an important role for synaptic transmission in the central nucleus of the amygdala (CeA) in mediating alcoholrelated behaviors and neuroadaptive mechanisms associated with alcohol dependence.Acute alcohol facilitates γ-aminobutyric acid (GABA)ergic transmission in the CeA via both pre-and postsynaptic mechanisms, and chronic alcohol increases baseline GABAergic transmission.Acute alcohol inhibits glutamatergic transmission via effects at N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the CeA, whereas chronic alcohol up-regulates NMDA receptor (NMDAR)-mediated transmission.Pro-(e.g., corticotropin-releasing factor [CRF]) and antistress (e.g., nociceptin/orphanin FQ, oxytocin) neuropeptides affect alcohol-and anxiety-related behaviors, and also alter the alcohol-induced effects on CeA neurotransmission.Alcohol dependence produces plasticity in these neuropeptide systems, reflecting a recruitment of those systems during the transition to alcohol dependence.A lcohol use disorder (AUD) is a global health problem.Alcoholism (i.e., dependence on alcohol) is a complex chronically relapsing disorder characterized by persistent alcoholseeking and alcohol-taking behaviors, loss of control in limiting intake (in terms of amount of drug per bout and number of drug-taking bouts), and the emergence of a withdrawal syndrome in the absence of the drug that includes, but is not limited to, dysphoria, sleep disturbances, disruption of autonomic processes, and increases in anxiety and irritability (ICD-10 and DSM-V).Preoccupation/anticipation, binge/in-toxication, and withdrawal/negative affect are three stages conceptualized as feeding into one another, becoming more intense over time, and ultimately leading to the pathological state known as addiction/dependence (Wise and Koob 2014).Decades of research have shaped the current view that excessive alcohol consumption is largely mediated by an organism's past experience with alcohol (e.g., intake pattern and frequency), and is driven by emotional disturbances rather than physical disturbances associated with alcohol withdrawal and abstinence

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Crossref · 10.1101/cshperspect.a039339

Cites

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Claims the paper makes

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  • Findingcitation

    CRF increases postsynaptic glutamate receptor function selectively in CRF1+ neurons.

    “but increases postsynaptic glutamate receptor functions selectively in CRF 1 + neurons”
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    • cites Wolfe et al. 2019

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  • Findingcitation

    CRF1- neurons do not display tonic inhibition.

    “In contrast, CRF 1 -neurons do not display tonic inhibition”
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    • cites Herman et al. 2013a

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  • Findingown data

    CRF at 25-200 nM decreases CeA EPSPs evoked locally or by BLA stimulation.

    “We found that CRF (25-200 nM) also decreased CeA EPSPs evoked locally or by BLA stimulation”
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    • cites Varodayan et al. 2017a

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  • Findingcitation

    CeA CRF1+ neurons are GABAergic.

    “CeA CRF 1 + neurons are GABAergic”
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    • cites Wolfe et al. 2019

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  • Findingcitation

    CeA CRF1+ neurons show no differences in mature spines.

    “CeA CRF 1 + neurons do not display differences in mature spines”
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    • cites Wolfe et al. 2019

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    Findingcitation

    Crhr1 has the highest coexpression with Penk and Sst and the least with Npy.

    “Crhr1 had the highest coexpression with Penk and Sst and the least with Npy”
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    Findingcitation

    LS CRF1- neurons show a tonic conductance after CIE that controls lack.

    “In contrast, LS CRF 1 -neurons showed a tonic conductance following CIE that was not observed in controls.”
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    • cites Herman et al. 2016

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    Findingown data

    Nociceptin decreases IPSP amplitude and completely blocks the CRF-induced increase in GABAergic transmission.

    “Nociceptin decreases the amplitude of IPSPs and completely blocks the CRF-induced increase in GABAergic transmission”
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    • cites Cruz et al. 2012

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    Findingcitation

    The NOP antagonist [Nphe1]nociceptin(1-13)NH2 blocks nociceptin-induced diminution of IPSCs but not CRF-induced augmentation of IPSCs.

    “the NOP receptor antagonist [Nphe 1 ]nociceptin(1-13) NH 2 blocked the nociceptin-induced diminution of IPSCs but not the CRF-induced augmentation of IPSCs”
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    • cites Cruz et al. 2012

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    Findingcitation

    Nociceptin prevents and reverses acute alcohol-induced increases in evoked IPSC amplitudes and mIPSC frequencies and decreases in PPF.

    “nociceptin both prevented (when applied before alcohol) and totally reversed (applied during alcohol) acute alcohol-induced increases in evoked IPSC amplitudes and mIPSC frequencies and decreases in PPF”
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    • cites Roberto and Siggins 2006

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    Findingcitation

    The antagonist blocks nociceptin-induced decreases in glutamatergic responses but does not affect ethanol-induced decreases in evoked EPSP amplitude.

    “The antagonist also blocked nociceptin-induced decreases in glutamatergic responses but did not affect ethanol-induced decreases in evoked EPSP amplitude.”
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    • cites Kallupi et al. 2014

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    Findingcitation

    Oxytocin inhibits evoked IPSPs in nondependent rats and increases PPF.

    “Oxytocin inhibited evoked IPSPs in nondependent rats, and increased PPF”
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    • cites Tunstall et al. 2019

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    Premisecitation

    Alcohol-dependent rats exhibit larger baseline-evoked CeA GABA A-mediated IPSP/C amplitudes, smaller baseline paired-pulse facilitation of evoked IPSCs, and higher baseline miniature IPSC frequency than alcohol-naive rats.

    “Alcoholdependent rats exhibit larger baseline-evoked CeA GABA A -mediated IPSP/C amplitudes, smaller baseline PPF of evoked IPSCs, and higher baseline frequency of mIPSCs compared to alcohol-naive rats.”
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    • cites Roberto et al. 2004a

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    Premisecitation

    Acute alcohol (5-66 mM) decreases excitatory postsynaptic potentials and currents in the CeA, mediated by both NMDAR and non-NMDAR mechanisms.

    “We demonstrated that acute alcohol (5-66 mM) decreases excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) in the CeA, and that these effects are mediated by both NMDAR and non-NMDAR mechanisms”
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    • cites Roberto et al. 2004b

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    Premisecitation

    GAT-3 expression is selectively decreased in the CeA of alcohol-dependent patients, suggesting a shared molecular mechanism for elevated CeA GABA transmission across species.

    “GAT-3 expression was also selectively decreased in the CeA of alcohol-dependent patients, suggesting a potential shared molecular mechanism for elevated CeA GABA transmission across species”
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    • cites Augier et al. 2018

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    Premisecitation

    Injection of GABA A antagonists into the three major extended amygdala regions suppressed alcohol drinking by nondependent rats, with the effect most potent and selective for alcohol when infused into the CeA.

    “Hyytiä and Koob (1995) found that injection of GABA A antagonists in the three major regions of the extended amygdala suppressed alcohol drinking by nondependent rats, but this effect was most potent and selective for alcohol when infused into”
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    • cites Hyytiä and Koob 1995

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    Premisecitation

    Chronic heavy consumption of drugs including alcohol promotes transition to dependence defined in part by dopamine down-regulation, glutamate hyperactivity, and brain stress system dysregulation.

    “Chronic consumption of large quantities of drugs, including alcohol, promotes a transition from casual drug use to drug dependence that is defined in part by down-regulation of dopamine signaling in the mesocorticolimbic reward system, hyperactivity of glutamate signaling, and dysregulation of brain stress systems”
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    • cites Koob and Zorrilla 2010

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    • cites Koob and Volkow 2016

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    Interpretationcitation

    PKCε facilitates alcohol-elicited vesicular GABA release and limits spontaneous GABA release in the CeA.

    “PKCε serves at least two roles in the CeA: (1) limiting baseline GABA release, and (2) facilitating alcohol-stimulated release of GABA.”
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    • cites Bajo et al. 2008

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    Premisecitation

    Chronic alcohol increases NR2B messenger RNA and/or protein levels in the CeA and BNST but not in other brain regions.

    “Chronic alcohol increases NR2B messenger RNA (mRNA) and/or protein levels (Roberto et al. 2006;Kash et al. 2009) in the CeA and BNST, but not in other brain regions”
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    • cites Roberto et al. 2006

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    • cites Kash et al. 2009

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    • cites Cebere et al. 1999

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    Interpretationcitation

    Chronic alcohol down-regulates the GABA B system in the CeA, which may explain increased GABAergic tone in dependent rats.

    “These effects of GABA B agonists and antagonists were absent or greatly attenuated in the CeA of alcohol-dependent rats, suggesting chronic alcohol-induced down-regulation of the GABA B system, which may explain the increased GABAergic tone observed in the CeA of dependent rats”
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    • cites Roberto et al. 2008

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    Premisenone given

    The CeA is implicated in anxiety, stress-related disorders, and the reinforcing effects of alcohol and other drugs of abuse.

    “The central nucleus of the amygdala (CeA) is a brain region implicated in anxiety, stress-related disorders, and the reinforcing effects of alcohol and other drugs of abuse.”
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    Premisenone given

    Prostress and antistress neuropeptides affect alcohol- and anxiety-related behaviors and alter alcohol-induced effects on CeA neurotransmission.

    “Pro-(e.g., corticotropin-releasing factor [CRF]) and antistress (e.g., nociceptin/orphanin FQ, oxytocin) neuropeptides affect alcohol-and anxiety-related behaviors, and also alter the alcohol-induced effects on CeA neurotransmission.”
    Quote in the paperSubstantial claim

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    Premisereasoning

    GABAergic transmission mediates some aspects of alcohol-drinking behavior, but the literature is ambiguous about the direction of these effects.

    “There is considerable evidence that GABAergic transmission mediates some aspects of alcohol-drinking behavior, but there is ambiguity in the literature with respect to the directions of these effects.”
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  • Classified as probably not a substantial claim.

    Premisecitation

    The extended amygdala comprises the CeA, the shell of the nucleus accumbens, and the lateral bed nucleus of the stria terminalis.

    “The major constituents of the extended amygdala are the CeA, the shell of the nucleus accumbens (NAc), and the lateral portion of the bed nucleus of the stria terminalis (BNST)”
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    • cites Heimer 1991

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    Premisecitation

    Systemic GABA A agonists increased voluntary alcohol drinking, whereas GABA A antagonists and benzodiazepine inverse agonists reduced alcohol intake.

    “Early studies showed that systemic administration of GABA A agonists increased voluntary alcohol drinking, whereas GABA A antagonists and benzodiazepine inverse agonists reduced alcohol intake”
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    • cites Boyle et al. 1993

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    Interpretationreasoning

    Chronic alcohol produces neuroadaptations in GABAergic neurotransmission and changes sensitivity to GABAergic compounds.

    “they suggest that (1) chronic alcohol produces neuroadaptations in GABAergic neurotransmission and changes sensitivity to GABAergic compounds”
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    Premisecitation

    Acute alcohol augments evoked IPSCs, decreases paired-pulse facilitation of evoked IPSCs, and increases miniature IPSC frequency in most CeA neurons, suggesting increased vesicular GABA release.

    “alcohol augments evoked inhibitory postsynaptic currents (IPSCs), decreases paired-pulse facilitation (PPF) of evoked IPSCs, and increases the frequency of miniature IPSCs (mIPSCs) (i.e., in tetrodotoxin [TTX] to eliminate action potential firing) in most CeA neurons, suggesting that alcohol increases vesicular GABA release”
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    • cites Roberto et al. 2003

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    • cites Varodayan et al. 2017b,c

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    Premisecitation

    Chronic alcohol exposure unmasks the ability of acute alcohol to increase presynaptic glutamate release in the CeA, an effect that persisted 2 weeks into abstinence.

    “Our laboratory found that chronic alcohol exposure unmasks the ability of acute alcohol to increase presynaptic glutamate release in the CeA (Roberto et al. 2004b), an effect that persisted 2 weeks into abstinence (Roberto et al. 2006).”
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    • cites Roberto et al. 2004b

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    Premisecitation

    The CeM receives prominent inputs from other amygdaloid nuclei, especially glutamatergic afferents from the BLA, and sends inhibitory projections to effector regions including hypothalamus, periaqueductal gray, locus coeruleus, and pedunculopontine tegmental nucleus.

    “By contrast, the CeM receives prominent inputs from other amygdaloid nuclei (especially glutamatergic afferents from BLA) and sends inhibitory projections to various effector regions (e.g., hypothalamus, periaqueductal gray, locus coeruleus, and pedunculopontine tegmental nucleus)”
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    Premisecitation

    CRF system dysregulation is implicated in anxiety, depression, addiction, PTSD, and eating disorders.

    “Dysregulation of the CRF system is implicated in numerous psychiatric disorders including anxiety, depression, addiction, posttraumatic stress disorder, and eating disorders”
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    • cites Menzaghi et al. 1994

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    • cites Koob 2003

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    • cites Valdez et al. 2003

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    Premisecitation

    The CeA is the major output center of the amygdala, and about 95% of CeA neurons are medium spiny GABAergic neurons.

    “The CeA is the major output center of the amygdala, and about 95% of CeA neurons are medium spiny GABAergic neurons”
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    • cites McDonald 1982

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    Premisecitation

    Extracellular CRF in the CeA rises after stress and after development of alcohol dependence.

    “Extracellular CRF levels in the CeA are elevated following exposure to stress and development of alcohol dependence”
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    • cites Merlo Pich et al. 1995

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    • cites Zorrilla et al. 2001

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    Premisecitation

    The CeL contains a higher density of neuropeptides than the CeM, receives cortical and thalamic input, and sends inhibitory inputs to the CeM, gating CeA output, as well as to distant regions such as the periaqueductal gray and paraventricular nucleus of the thalamus.

    “The CeL contains a much higher density of neuropeptides (e.g., dynorphin, CRF [Veening et al. 1984;Cassell et al. 1986;Shimada et al. 1989;Pomrenze et al. 2015;Wolfe et al. 2019]) than the CeM, receives input from cortex and thalamus, and sends inhibitory inputs to the CeM, thereby gating the output activity of the CeA, but also to more distant brain regions such as the periaqueductal gray and par”
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    • cites Penzo et al. 2014

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    Premisecitation

    The CeA is not homogeneous and can be subdivided into lateral and medial aspects that differ in neuropeptide content, afferents, and efferent targets.

    “The CeA is not a homogeneous neuroanatomical structure, and can be subdivided into lateral (CeL) and medial (CeM) aspects that differ in neuropeptide content, origin of afferents, and target sites of efferent projections”
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    • cites Sun et al. 1991

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    Premisecitation

    CRF2 receptor activation is associated with decreased feeding.

    “CRF 2 receptor activation has been associated with decreased feeding”
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    Premisecitation

    SNPs rs10055255, rs10062367, and rs7728378 in CRHBP are each associated with increased risk of alcohol drinking and/or anxiety in AUD patients.

    “Single-nucleotide polymorphisms (SNPs) in the CRHBP (10 kD) fragment, rs10055255, rs10062367, and rs7728378 were each associated with increased risk of alcohol drinking and/or anxiety in patients with AUD”
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    • cites Haass-Koffler et al. 2016

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    Premisecitation

    The CRHBP rs1875999 locus is associated with risk for cocaine and heroin addiction in African-Americans.

    “the CRHBP rs1875999 locus is associated with risk for both cocaine and heroin addiction in African-Americans”
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    • cites Levran et al. 2014a,b

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    Premisecitation

    CRF-BP-containing terminals colocalize with CRF-positive cell bodies, supporting a regulatory interaction.

    “terminals containing CRF-BP colocalize with CRF-positive cell bodies supporting their regulatory interaction”
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    • cites Westphal and Seasholtz 2006

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    Premisecitation

    Rats bred for high alcohol preference show increased anxiety-like behavior and CRF1 levels.

    “rats bred for high alcohol preference show increased anxiety-like behavior and CRF 1 levels”
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    • cites Ciccocioppo et al. 2006

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    Premisecitation

    CRF-BP binds CRF with equal or greater affinity than CRFRs, limiting bioavailability and acting as an endogenous negative regulator of CRF signaling.

    “CRF-binding protein (CRF-BP) binds CRF with equal or greater affinity than do CRFRs, limiting its bioavailability and serving as an endogenous negative regulator of CRF signaling”
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    • cites Potter et al. 1992

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    Premisecitation

    N/OFQ and NOP are widely expressed in the brain.

    “The neuropeptide nociceptin/orphanin FQ (N/ OFQ) (Meunier et al. 1995;Reinscheid et al. 1995;Meunier 1997) and its cognate receptor nociceptin opioid peptide (NOP) are widely expressed in the brain”
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    Interpretationcitation

    The mechanisms of CRF-induced glutamate facilitation are complex and may involve both CRF1 and CRF2 with opposite effects.

    “but the mechanisms are complex and may involve both CRF 1 and CRF 2 receptors with opposite receptor subtype effects on glutamate release”
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    • cites Varodayan et al. 2017a

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    Interpretationreasoning

    Nociceptin modulates both ethanol and CRF effects through NOP receptors.

    “indicating that nociceptin modulates both ethanol and CRF effects through the NOP receptors”
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    • cites Cruz et al. 2012

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    Premisecitation

    In response to stress, oxytocin is released into the bloodstream via the posterior pituitary and to extrahypothalamic brain regions including the extended amygdala, where it decreases anxiety and stress.

    “In response to stress, oxytocin is released both into the bloodstream via the posterior pituitary and to many extrahypothalamic brain regions including the extended amgydala, where it decreases anxiety and stress”
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    • cites Kasting 1988

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    Premisecitation

    Oxytocin reaches the brain after intraperitoneal and intranasal administration in rodents and intravenous and intranasal administration in macaques.

    “oxytocin reaches the brain following both intraperitoneal and intranasal administration in rodents (Neumann et al. 2013;Tanaka et al. 2018) and intravenous and intranasal administration in macaques”
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    • cites Neumann et al. 2013

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    • cites Tanaka et al. 2018

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    • cites Lee et al. 2018

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    Premisecitation

    Exogenous oxytocin reduces consumption, withdrawal symptoms, and relapse for stimulants, opioids, and alcohol in animal models.

    “Exogenous oxytocin administered to animal models has been found to reduce consumption, withdrawal symptomology, and relapse associated with many drugs of abuse, including stimulants, opioids, and alcohol”
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    • cites Lee and Davis 1997

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    Interpretationcitation

    Acute stress and alcohol dependence increase nociceptin system function in the CeA.

    “These combined results demonstrate that acute stress and alcohol dependence increase nociceptin system function in the CeA”
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    • cites Ciccocioppo et al. 2014a

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    Premisecitation

    Oxytocin is involved in many biological processes and has a purported antistress role in the brain.

    “The neuropeptide oxytocin is involved in many biological processes and has a purported antistress role in the brain”
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    • cites Lang et al. 1983

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    Premisecitation

    Oxytocin is primarily expressed in PVN and SON neurons of the hypothalamus.

    “Oxytocin is primarily expressed in neurons of the PVN and supraoptic nuclei (SON) of the hypothalamus”
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    • cites Huber et al. 2005

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    • cites Stoop 2012

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    Premisecitation

    Oxytocin has been suggested as a putative treatment for addiction.

    “Oxytocin has also been suggested as a putative treatment for addiction”
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    • cites Kovács et al. 1998

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    Premisecitation

    Intranasal oxytocin reduces alcohol craving, consumption, and withdrawal symptoms in alcohol-dependent patients.

    “intranasal oxytocin administration has been found to reduce alcohol craving, consumption, and withdrawal symptoms in alcohol-dependent patients”
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    • cites Pedersen et al. 2013

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    • cites Mitchell et al. 2016

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    • cites Hansson et al. 2018

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    Interpretationcitation

    The nociceptin system regulates glutamatergic transmission and interacts complexly with ethanol at CeA glutamatergic synapses.

    “Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses”
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    • cites Kallupi et al. 2014

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    Interpretationreasoning

    Neuropeptides present at high levels in the CeA profoundly alter inhibitory transmission, and potentially also excitatory transmission.

    “Neuropeptides present at high levels in the CeA profoundly alter inhibitory transmission, and potentially also excitatory transmission.”
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    Interpretationown data

    Drug effects on synaptic transmission in the CeA may reliably predict therapeutic testing for anxiety and AUDs.

    “Our understanding of this pivotal system as a”
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    Interpretationreasoning

    Neuropeptide systems are recruited and/or up-regulated during the transition to alcohol dependence, a dynamic disease defined largely by a negative emotional state in the absence of the drug.

    “This point also enhances our understanding of why these neuropeptide systems are recruited and/or up-regulated during the transition to alcohol dependence, a dynamic disease defined largely by a negative emotional state in the absence of the drug.”
    Quote in the paperSubstantial claim

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    Interpretationcitation

    Alcohol may alter release of local opioids, endocannabinoids, and/or NPY in the CeA, which may increase GABA-mediated inhibition of downstream target areas.

    “alcohol may alter the release of local opioids (Lam et al. 2008;Gilpin et al. 2014), endocannabinoids (Roberto et al. 2010;Kirson et al. 2018), and/or NPY (Gilpin et al. 2008a,b;Gilpin and Roberto 2012) in CeA that in turn may increase GABA-mediated inhibition of downstream target areas.”
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    • cites Lam et al. 2008

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    • cites Gilpin et al. 2014

      Not checked in the free run.

    • cites Roberto et al. 2010

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Increases or decreases in inhibitory output from the CeA to downstream effector regions may decrease or increase anxiety-like behavior, respectively.

    “Thus, increases or decreases in inhibitory output from the CeA to downstream effector regions may decrease or increase anxiety-like behavior, respectively”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Paré et al. 2004

      Not checked in the free run.

    • cites Davis et al. 2010

      Not checked in the free run.

    • cites Tye et al. 2011

      Not checked in the free run.

52 of 52

  • The paper relies on this without support.

    The oxytocin receptor is expressed throughout the brain and peripheral systems.

    “as the oxytocin receptor (OXTR) is expressed throughout the brain and peripheral systems”

  • The paper relies on this without support.

    Most neurons in the CeA are GABAergic inhibitory projection neurons or interneurons that cotransmit GABA and one or more neuropeptides.

    “most neurons in the CeA are GABAergic inhibitory projection neurons or interneurons that cotransmit GABA and one or more neuropeptides”
2 of 2

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?

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. 2005, Ethanol-CRF interactions at GABAergic synapses in rat central amygdala, Alcohol Clin Exp Res Suppl, 29, 26

Cited by

Sorted by citations

Related

Authors
Roberto, M., Kirson, D., & Khom, S.
Affiliations
Scripps Research Institute (US)
Corresponding author
Roberto, Marisa
ORCID
Venue
Cold Spring Harbor Perspectives in Medicine
Publisher
Cold Spring Harbor Laboratory
Published
2020-01-27
Volume
11
Issue
2
Pages
a039339
ISSN
2157-1422 (ISSN-L)
DOI
10.1101/cshperspect.a039339
PMC
PMC7382982
OpenAlex
W3003468827
Cited by
112
References
238
Citations by year
2026: 16 · 2025: 24 · 2024: 17 · 2023: 10 · 2022: 23 · 2021: 16 · 2020: 6
Type
posted content
Language
en
Open access
Locations
  • Cold Spring Harbor Perspectives in Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
  • National Institutes of Health (5r37aa017447-15)
  • National Institute on Alcohol Abuse and Alcoholism (R37-AA017447, R01AA021491, R01AA016985, K99AA026638, R01AA015566, P50AA006420, R00AA026638, R01AA027700, R01AA017447, U01AA013498, P60AA006420)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
alcoholism, central amygdala, GABAergic neurotransmission, glutamatergic neurotransmission, NMDA receptor, AMPA receptors, neural adaptation, corticotropin-releasing factor, nociceptin/orphanin FQ, oxytocin, neuropeptides, alcohol withdrawal, anxiety, synaptic plasticity
MeSH terms
Nociceptin, Ethanol, Alcoholism, Animals, Humans, Synaptic Transmission, Oxytocin, Receptors, GABA-A, Receptors, N-Methyl-D-Aspartate, Opioid Peptides, Central Amygdaloid Nucleus

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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.

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