CoChat
Sign Up
Cited by 244Neurotransmitter Receptor Influence on BehaviorMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 163 of the 163 references it cites were found in a registry or an index.

Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction

Open access
Sharp, B M·2017·Translational Psychiatry
DOI 10.1038/tp.2017.161PMC PMC5611728
Open this paper in CoChat — free accountOpen PDF

Abstract

The amygdala integrates and processes incoming information pertinent to reward and to emotions such as fear and anxiety that promote survival by warning of potential danger. Basolateral amygdala (BLA) communicates bi-directionally with brain regions affecting cognition, motivation and stress responses including prefrontal cortex, hippocampus, nucleus accumbens and hindbrain regions that trigger norepinephrine-mediated stress responses. Disruption of intrinsic amygdala and BLA regulatory neurocircuits is often caused by dysfunctional neuroplasticity frequently due to molecular alterations in local GABAergic circuits and principal glutamatergic output neurons. Changes in local regulation of BLA excitability underlie behavioral disturbances characteristic of disorders including post-traumatic stress syndrome (PTSD), autism, attention-deficit hyperactivity disorder (ADHD) and stress-induced relapse to drug use. In this Review, we discuss molecular mechanisms and neural circuits that regulate physiological and stress-induced dysfunction of BLA/amygdala and its principal output neurons. We consider effects of stress on motivated behaviors that depend on BLA; these include drug taking and drug seeking, with emphasis on nicotine-dependent behaviors. Throughout, we take a translational approach by integrating decades of addiction research on animal models and human trials. We show that changes in BLA function identified in animal addiction models illuminate human brain imaging and behavioral studies by more precisely delineating BLA mechanisms. In summary, BLA is required to promote responding for natural reward and respond to second-order drug-conditioned cues; reinstate cue-dependent drug seeking; express stress-enhanced reacquisition of nicotine intake; and drive anxiety and fear. Converging evidence indicates that chronic stress causes BLA principal output neurons to become hyperexcitable.

Overview

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/tp.2017.161

Cites

163 of 163 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Schematic representation of neural projections from multiple brain regions to basolateral amygdala (BLA). The primary neurotransmitters are identified. DRN, dorsal raphe nucleus; NTS, nucleus tractus solitarius; SN, substantia nigra; VTA, ventral tegmental area.
Figure 1 Schematic representation of neural projections from multiple brain regions to basolateral amygdala (BLA). The primary neurotransmitters are identified. DRN, dorsal raphe nucleus; NTS, nucleus tractus solitarius; SN, substantia nigra; VTA, ventral tegmental area.CC BY-NC-ND · PubMed Central
Figure 2 Schematic representation of GABA, glutamate and dopamine neural inputs to a GABA interneuron (solid blue) regulating a basolateral amygdala (BLA) principal neuron (solid green) and directly to the principal neuron. The pre- and postsynaptic excitatory (+) and inhibitory (−) effects of each neurotransmitter are shown, as are the glutamate and dopamine projections to BLA.
Figure 2 Schematic representation of GABA, glutamate and dopamine neural inputs to a GABA interneuron (solid blue) regulating a basolateral amygdala (BLA) principal neuron (solid green) and directly to the principal neuron. The pre- and postsynaptic excitatory (+) and inhibitory (−) effects of each neurotransmitter are shown, as are the glutamate and dopamine projections to BLA.CC BY-NC-ND · PubMed Central
Figure 3 Repeated stress during abstinence increased the reacquisition of operant nicotine self-administration (SA). The reacquisition of nicotine SA was measured under a progressive ratio (PR) schedule begun immediately after the final stress on day 7 (30 min sessions of restraint in a plexiglass cylinder on days 1, 3, 5 and 7 of abstinence from nicotine SA) and followed by an FR5 (fixed ratio: 5 operant lever presses required to obtain 1 infusion of nicotine) schedule. (a) The number of nicotine injections and the final ratio completed under a PR schedule during a 23-h session of reacquisition were significantly increased by repeated restraint stress compared with the non-stress group. (b, c) After the PR session, both nicotine injections and active lever presses during 5 days of reacquisition under an FR5 schedule were also significantly increased by stress (repeated measure ANOVA: P<0.05). *P<0.05 versus non-stress groups (t-test). #P<0.05 versus baseline during the final 3 days of acquisition within group; †P<0.05 stress versus non-stress group at same time interval (t-test). n=5 and 7 for non-stress and stress groups, respectively. Reprinted from Yu et al.147 with permission from the publisher.
Figure 3 Repeated stress during abstinence increased the reacquisition of operant nicotine self-administration (SA). The reacquisition of nicotine SA was measured under a progressive ratio (PR) schedule begun immediately after the final stress on day 7 (30 min sessions of restraint in a plexiglass cylinder on days 1, 3, 5 and 7 of abstinence from nicotine SA) and followed by an FR5 (fixed ratio: 5 operant lever presses required to obtain 1 infusion of nicotine) schedule. (a) The number of nicotine injections and the final ratio completed under a PR schedule during a 23-h session of reacquisition were significantly increased by repeated restraint stress compared with the non-stress group. (b, c) After the PR session, both nicotine injections and active lever presses during 5 days of reacquisition under an FR5 schedule were also significantly increased by stress (repeated measure ANOVA: P<0.05). *P<0.05 versus non-stress groups (t-test). #P<0.05 versus baseline during the final 3 days of acquisition within group; †P<0.05 stress versus non-stress group at same time interval (t-test). n=5 and 7 for non-stress and stress groups, respectively. Reprinted from Yu et al.147 with permission from the publisher.CC BY-NC-ND · PubMed Central
Figure 4 Reversible disconnection of basolateral amygdala (BLA) and nucleus accumbens core (NAcc) blocked the expression of stress-enhanced operant nicotine self-administration (SA) during reacquisition. GABA receptor agonists, baclofen and muscimol (B+M), or vehicle, were microinjected unilaterally into BLA and contralaterally into NAcc 30 min prior to reacquisition sessions on d1 and 2 (indicated by arrows). Active lever presses and nicotine injections are shown in a, b, respectively. *P<0.05 for within-group comparisons of responses during reacquisition versus the final 3d of acquisition (one-way ANOVA with post hoc Bonferroni comparisons); #P< 0.05 for stress/B+M versus stress/vehicle on the same d (t-test). Reprinted from Yu and Sharp148 with permission from the publisher.
Figure 4 Reversible disconnection of basolateral amygdala (BLA) and nucleus accumbens core (NAcc) blocked the expression of stress-enhanced operant nicotine self-administration (SA) during reacquisition. GABA receptor agonists, baclofen and muscimol (B+M), or vehicle, were microinjected unilaterally into BLA and contralaterally into NAcc 30 min prior to reacquisition sessions on d1 and 2 (indicated by arrows). Active lever presses and nicotine injections are shown in a, b, respectively. *P<0.05 for within-group comparisons of responses during reacquisition versus the final 3d of acquisition (one-way ANOVA with post hoc Bonferroni comparisons); #P< 0.05 for stress/B+M versus stress/vehicle on the same d (t-test). Reprinted from Yu and Sharp148 with permission from the publisher.CC BY-NC-ND · PubMed Central

Verification

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 160 references

Research works printed but not linked: 2

  1. Martin BS, Corbin JG, Huntsman MM . Deficient tonic GABAergic conductance and synaptic balance in the fragile X syndrome amygdala. J Neurophysiol 2014; 112: 891–902. · DOI
  2. Fallon J, Ciofi P . Distribution of Monoamines within the Amygdala. IA J (ed). Academic Press: New York, 1992.

Cited by

Sorted by citations

See all 244

Related

Metadata

Authors
Sharp, B. M.
Affiliations
University of Tennessee Health Science Center (US)
Corresponding author
Sharp, B M
ORCID
Sharp, B M
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-08-08
Volume
7
Issue
8
Pages
e1194-e1194
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2017.161
PMC
PMC5611728
OpenAlex
W2743494055
Cited by
244
References
160
Citations by year
2026: 19 · 2025: 26 · 2024: 31 · 2023: 34 · 2022: 33 · 2021: 41 · 2020: 30 · 2019: 19 · 2018: 10 · 2017: 1
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
basolateral amygdala, motivated behavior, addiction, nicotine dependence, drug-seeking behavior, drug relapse, chronic stress, principal neurons, GABAergic circuits, anxiety, fear, post-traumatic stress disorder, autism spectrum disorder, attention deficit hyperactivity disorder, cue reactivity
MeSH terms
Animals, Humans, Motivation, Neurons, Stress, Psychological, Behavior, Addictive, Drug-Seeking Behavior, Basolateral Nuclear Complex

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