Interaction of the Basolateral Amygdala and Orbitofrontal Cortex is Critical for Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

Lasseter, Heather C; Wells, Audrey M; Xie, Xiaohu; Fuchs, Rita A

doi:10.1038/npp.2010.209

Cited by 72Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesMemory and Neural Mechanisms

Interaction of the Basolateral Amygdala and Orbitofrontal Cortex is Critical for Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

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Lasseter, Heather C, Wells, Audrey M, Xie, Xiaohu, Fuchs, Rita A·2011·Neuropsychopharmacology

DOI 10.1038/npp.2010.209PMC PMC3020992

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Abstract

The basolateral amygdala (BLA) and lateral orbitofrontal cortex (OFC) are critical elements of the neural circuitry that regulates drug context-induced reinstatement of cocaine-seeking behavior. Given the existence of dense reciprocal anatomical connections between these brain regions, this study tested the hypothesis that serial information processing by the BLA and OFC is necessary for drug context-induced cocaine-seeking behavior. Male Sprague-Dawley rats were trained to lever press for un-signaled cocaine infusions (0.15 mg/infusion, i.v.) in a distinct environment (cocaine-paired context) then underwent extinction training in a different environment (extinction context). During four subsequent test sessions, rats were re-exposed to the cocaine-paired and extinction contexts in order to assess cocaine-seeking behavior (non-reinforced active lever responding). Immediately before each test session, rats received microinfusions of the GABA(A)/GABA(B) agonist cocktail, baclofen+muscimol (BM: 1.0/.01 mM), or vehicle unilaterally into the BLA plus the contralateral or ipsilateral OFC, or unilaterally into the OFC alone. Exposure to the previously cocaine-paired context, but not the extinction context, reinstated extinguished cocaine-seeking behavior. BM-induced unilateral OFC inactivation failed to alter this behavior, similar to the effect of unilateral BLA inactivation in our previous study (Fuchs et al, 2007). Conversely, neural inactivation of the BLA plus the contralateral or ipsilateral OFC equally attenuated drug context-induced cocaine seeking without altering food-reinforced instrumental responding, relative to vehicle pretreatment. These findings suggest that the BLA and OFC co-regulate drug context-induced motivation for cocaine either through sequential information processing via intra- and interhemispheric connections or by providing converging input to a downstream brain region.

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Amygdala and OFC projections to DA neurons and NAc are involved in conditioned responses to food and drugs.
“projections from the amygdala and the OFC to DA neurons and to NAc are involved in conditioned responses to food (53) and drugs (54,55).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [54]
Projections from amygdala, hippocampus, and OFC to DA neurons and NAc are involved in conditioned responses to food and drugs.
“More specifically, projections from the amygdala, hippocampus, and OFC to DA neurons and to NAc are involved in conditioned responses to food (52) and drugs (53).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [53]

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Involvement of a mesocorticolimbic subcircuit in the reinstatement of drug context-induced cocaine seeking behavior in rats
Lasseter, H. C. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/f844-m990
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The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats
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Authors: Lasseter, H. C., Wells, A. M., Xie, X., & Fuchs, R. A.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Fuchs, Rita A
ORCID: Lasseter, Heather C
Xie, Xiaohu
Fuchs, Rita A
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2010-12-01
Volume: 36
Issue: 3
Pages: 711-720
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2010.209
PMC: PMC3020992
OpenAlex: W1999255392
Cited by: 72
References: 72
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 10 · 2019: 2 · 2018: 10 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 10 · 2012: 5
FWCI: 2.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: National Institute on Drug Abuse (DA025646, DA025617, R01DA025617, R01DA017673, R01DA025646, F31DA028051, T32DA007244)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: cocaine-seeking behavior, reinstatement, basolateral amygdala, orbitofrontal cortex, GABAergic inhibition, baclofen, muscimol, neural inactivation, extinction, interhemispheric connections
MeSH terms: Amygdala, Analysis of Variance, Animals, Behavior, Animal, Cocaine, Conditioning, Operant, Extinction, Psychological, Food, Male, Motor Activity, Reinforcement, Psychology, Self Administration, Rats, Sprague-Dawley, Prefrontal Cortex, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Rats

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Interaction of the Basolateral Amygdala and Orbitofrontal Cortex is Critical for Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

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