Neural substrates of cocaine-cue associations that trigger relapse
Abstract
Learned associations that occur during the process of repeated drug use in addiction can later manifest as trigger factors in relapse to renewed drug-seeking and drug-taking behavior. The process of conditioned-cued relapse of drug-seeking behavior has been successfully modeled in animals using the reinstatement procedure, in which chronic drug self-administration can be extinguished or withheld, and then reinstated using conditioned stimuli previously paired with the drug. Our laboratory has extensively studied the neural circuitry underlying conditioned-cued drug-seeking during the expression of reinstatement. In order to study the learning process of drug-cue pairings, we further developed a procedure whereby discrete cocaine-cue pairings can be conducted in a single pavlovian training session in animals previously trained to self-administer cocaine. Presentation of these cues during later reinstatement trials produces robust responding over extinction levels at levels similar to those seen when animals experience the cues on a daily basis. In a series of experiments, we have shown that reversible pharmacological inactivation of the basolateral complex of the amygdala just prior to acquisition of cocaine-cue associations blocks the ability of cocaine-paired stimuli to elicit conditioned-cued reinstatement. This learning process is mediated in part by muscarinic acetylcholine and dopaminergic inputs to the basolateral complex of the amygdala, as intra-amygdala infusion of selective receptor antagonists at the time of acquisition significantly affects reinstatement. We have also recently found that disruption of neural activity within the basolateral complex of the amygdala at the time of consolidation (just after cocaine-cue pairings) will disrupt reinstatement. Taken together, these results reveal the importance of the amygdala in the acquisition, consolidation, and expression of drug-stimulus learning that drives relapse to drug-seeking behavior.
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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 [55]
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- Authors
- See, R. E.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- See, Ronald E.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 526
- Issue
- 1-3
- Pages
- 140-146
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2069865220
- Cited by
- 228
- References
- 74
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 19 · 2012: 19
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA15369, DA16511, R01DA010462, P50DA015369, DA10462)
- 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, relapse, reinstatement, drug-seeking behavior, basolateral amygdala, classical conditioning, muscarinic receptors, dopaminergic input, memory consolidation, extinction, addiction
- MeSH terms
- Amygdala, Animals, Association Learning, Brain, Cocaine, Conditioning, Operant, Cues, Recurrence, Substance-Related Disorders
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