Basolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits
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In the development of addiction, drug seeking becomes habitual and controlled by drug-associated cues, and the neural locus of control over behaviour shifts from the ventral to the dorsolateral striatum. The neural mechanisms underlying this functional transition from recreational drug use to drug-seeking habits are unknown. Here we combined functional disconnections and electrophysiological recordings of the amygdalo-striatal networks in rats trained to seek cocaine to demonstrate that functional shifts within the striatum are driven by transitions from the basolateral (BLA) to the central (CeN) amygdala. Thus, while the recruitment of dorsolateral striatum dopamine-dependent control over cocaine seeking is triggered by the BLA, its long-term maintenance depends instead on the CeN. These data demonstrate that limbic cortical areas both tune the function of cognitive territories of the striatum and thereby underpin maladaptive cocaine-seeking habits.
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Both amygdala subregions and DMS participate in drug-seeking and active-avoidance behavior.
“Both amygdala subregions and DMS participate in drug-seeking66,73,74 and active-avoidance behavior75.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [66]
The transition of behavioral control to habit systems requires a shift of behavioral control from BLA to CeA.
“Indeed, the transition of behavioral control to habit systems requires a shift of behavioral control from BLA to CeA66.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [66]
The CeA can work indirectly via the midbrain with the dorsolateral striatum to regulate habit formation.
“The CeA can also work indirectly, likely via the midbrain67,68, with the dorsolateral striatum to regulate habit formation32,66.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [66]
The central amygdala is particularly implicated in compulsive drug seeking and drug seeking after extended use, dependence and withdrawal, or stress.
“The central amygdala is particularly implicated in compulsive drug seeking and drug seeking after extended use, dependence and withdrawal, or stress66,76.”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [66]
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- Authors
- Murray, J. E., Belin-Rauscent, A., Simon, M., Giuliano, C., Benoit-Marand, M., Everitt, B. J., & Belin, D.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Everitt, Barry J.
- Belin, David
- Venue
- Nature Communications
- Published
- 2015-12-14
- Volume
- 6
- Issue
- 1
- Pages
- 10088-10088
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4682035
- OpenAlex
- W2258184930
- Cited by
- 97
- References
- 71
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 3 · 2021: 6 · 2020: 15 · 2019: 16 · 2018: 13 · 2017: 7 · 2016: 7
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (093875)
- University of Cambridge
- Agence Nationale de la Recherche (ANR12 SAMA00201, ANR-12-SAMA-0002)
- Institut National de la Santé et de la Recherche Médicale
- AXA Research Fund
- Université de Poitiers
- Medical Research Council (9536855)
- 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 › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine seeking, cocaine dependence, basolateral amygdala, central amygdala, dorsolateral striatum, functional disconnection, dopamine, cue reactivity
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Isoxazoles, Male, Self Administration, Tetrazoles, N-Methylaspartate, Rats, Sprague-Dawley, Receptors, Glutamate, Excitatory Amino Acid Antagonists, Rats, Drug-Seeking Behavior, Basolateral Nuclear Complex, Central Amygdaloid Nucleus
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