A large-scale c-Fos brain mapping study on extinction of cocaine-primed reinstatement
Neuropsychopharmacol.. 2024-04-25; :
DOI: 10.1038/s41386-024-01867-6
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1. Neuropsychopharmacology. 2024 Apr 25. doi: 10.1038/s41386-024-01867-6. Online
ahead of print.
A large-scale c-Fos brain mapping study on extinction of cocaine-primed
reinstatement.
Lenoir M(#)(1), Engeln M(#)(2), Navailles S(3), Girardeau P(4), Ahmed SH(5).
Author information:
(1)Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France.
.
(2)Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France.
.
(3)Thales, 33700, Mérignac, France.
(4)Univ. Bordeaux, UFR des Sciences Odontologiques, Bordeaux, France.
(5)Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France.
(#)Contributed equally
Individuals with cocaine addiction can experience many craving episodes and
subsequent relapses, which represents the main obstacle to recovery. Craving is
often favored when abstinent individuals ingest a small dose of cocaine,
encounter cues associated with drug use or are exposed to stressors. Using a
cocaine-primed reinstatement model in rat, we recently showed that
cocaine-conditioned interoceptive cues can be extinguished with repeated cocaine
priming in the absence of drug reinforcement, a phenomenon we called extinction
of cocaine priming. Here, we applied a large-scale c-Fos brain mapping approach
following extinction of cocaine priming in male rats to identify brain regions
implicated in processing the conditioned interoceptive stimuli of cocaine
priming. We found that cocaine-primed reinstatement is associated with increased
c-Fos expression in key brain regions (e.g., dorsal and ventral striatum,
several prefrontal areas and insular cortex), while its extinction mostly
disengages them. Moreover, while reinstatement behavior was correlated with
insular and accumbal activation, extinction of cocaine priming implicated parts
of the ventral pallidum, the mediodorsal thalamus and the median raphe. These
brain patterns of activation and inhibition suggest that after repeated priming,
interoceptive signals lose their conditioned discriminative properties and that
action-outcome associations systems are mobilized in search for new
contingencies, a brain state that may predispose to rapid relapse.
© 2024. The Author(s), under exclusive licence to American College of
Neuropsychopharmacology.
DOI: 10.1038/s41386-024-01867-6
PMID: 38664549