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

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Sharp, B M·2017·Translational Psychiatry

DOI 10.1038/tp.2017.161PMC PMC5611728

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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.

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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
Fallon J, Ciofi P . Distribution of Monoamines within the Amygdala. IA J (ed). Academic Press: New York, 1992.

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“correspondence to match each section to its corresponding ARA atlas template, (2) to warp data sections to atlas templates, (3) to threshold labeling, (4)”
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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: gold
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0 (tdm)
creativecommons.org/licenses/by-nc-nd/4.0 (vor)
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

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

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