Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats.
Cereb. Cortex. 2014-05-28; 25(9): 3167-3181
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1. Cereb Cortex. 2015 Sep;25(9):3167-81. doi: 10.1093/cercor/bhu112. Epub 2014 May
Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine
and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats.
Navailles S(1), Guillem K(1), Vouillac-Mendoza C(1), Ahmed SH(1).
(1)Institut des Maladies Neurodégénératives, CNRS UMR 5293, Université de
Bordeaux, Bordeaux F-33000, France.
People with cocaine addiction retain some degree of prefrontal cortex (PFC)
inhibitory control of cocaine craving, a brain capacity that may underlie the
efficacy of cognitive behavioral therapy for addiction. Similar findings were
recently found in rats after extended access to and escalation of cocaine
self-administration. Rats’ inhibitory control of cocaine seeking was flexible,
sufficiently strong to suppress cocaine-primed reinstatement and depended, at
least in part, on neuronal activity within the prelimbic (PL) PFC. Here, we used
a large-scale and high-resolution Fos mapping approach to identify, beyond the PL
PFC, how top-down and/or bottom-up PFC-subcortical circuits are recruited during
inhibition of cocaine seeking. Overall, we found that effective inhibitory
control of cocaine seeking is associated with the coordinated recruitment of
different top-down cortical-striatal circuits originating from different PFC
territories, and of different bottom-up dopamine (DA) and serotonin (5-HT)
midbrain subsystems that normally modulate activity in these circuits. This
integrated brain response suggests that rats concomitantly engage and experience
intricate cognitive and affective processes when they have to inhibit intense
cocaine seeking. Thus, even after extended drug use, rats can be successfully
trained to engage whole-brain inhibitory control mechanisms to suppress cocaine
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PMID: 24872521 [Indexed for MEDLINE]