Cited by 69Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeuroscience and Neuropharmacology Research

Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization

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Brown, Robyn Mary, Short, Jennifer Lynn, Lawrence, Andrew John·2010·PLoS ONE

Abstract

Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice.

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Crossref · 10.1371/journal.pone.0015889

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  • Activation of the habenula in animal models of cocaine addiction has been associated with relapse to drug taking upon cue exposure.

    “Indeed, activation of the habenula, in animal models of cocaine addiction, has been associated with relapse to drug taking upon cue exposure (153,154).”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [154]

  • In animal models of cocaine or heroin addiction, activation of the lateral habenula is associated with relapse.

    “Indeed, activation of the lateral habenula, in animal models of cocaine or heroin addiction, has been associated with relapse (108,109).”

    From The Addictive Dimensionality of Obesity (2013) · cites this paper as [109]

  • Activation of the habenula in cocaine addicted subjects has been associated with behavioral relapse to drug taking upon cue exposure.

    “Indeed, activation of the habenula, in cocaine addicted subjects, has been associated with behavioral relapse to drug taking upon cue exposure (Brown et al 2011;Zhang et al 2005).”

    From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Brown et al 2011

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Authors
Brown, R. M., Short, J. L., & Lawrence, A. J.
Affiliations
The University of Melbourne (AU)
Corresponding author
Lawrence, Andrew John
Venue
PLoS ONE
Published
2010-12-29
Volume
5
Issue
12
Pages
e15889
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2093084898
Cited by
69
References
83
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 4 · 2013: 11 · 2012: 6
FWCI
3.23
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • State Government of Victoria
  • National Health and Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
cocaine, reinstatement, conditioned place preference, drug-seeking behavior, relapse, drug sensitization, lateral habenula, Fos expression, neuronal activation, extinction, addiction
MeSH terms
Animals, Behavior, Animal, Brain, Cell Nucleus, Cocaine, Conditioning, Psychological, Conditioning, Operant, Immunohistochemistry, Male, Neurons, Reinforcement, Psychology, Behavior, Addictive, Proto-Oncogene Proteins c-fos, Mice

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