Discriminative inhibitory control of cocaine seeking involves the prelimbic prefrontal cortex.
Biological Psychiatry. 2013-02-01; 73(3): 271-279
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1. Biol Psychiatry. 2013 Feb 1;73(3):271-9. doi: 10.1016/j.biopsych.2012.08.011.
Epub 2012 Sep 15.
Discriminative inhibitory control of cocaine seeking involves the prelimbic
Mihindou C(1), Guillem K, Navailles S, Vouillac C, Ahmed SH.
(1)Université de Bordeaux and the Centre National de la Recherche Scientifique,
Institut des Maladies Neurodégénératives, Bordeaux, France.
BACKGROUND: Recent neuroimaging studies have shown that people with cocaine
addiction retain some degree of control over drug craving that correlates with
neural activity in the lateral prefrontal cortex (PFC). Here, we report similar
findings in a rat model of inhibitory control of cocaine seeking.
METHODS: Rats actively responding for cocaine were trained to stop responding
when presented with a discriminative stimulus that signaled lack of
reinforcement. Rats were then tested for inhibitory control of cocaine seeking in
novel behavioral contexts and in circumstances when cocaine seeking is
particularly intense (e.g., following drug priming). The role of neuronal
activity in different subregions of the PFC was assessed using local
pharmacologic inactivation and c-Fos immunohistochemistry.
RESULTS: Rats progressively acquired the ability to stop cocaine seeking, even
during drug intoxication and after a long history of cocaine self-administration.
Inhibitory control of cocaine seeking was flexible, sufficiently strong to block
cocaine-primed reinstatement, and selectively depended on increased neuronal
activity within the prelimbic PFC, which is considered the rodent functional
homolog of the human lateral PFC.
CONCLUSIONS: Parallel evidence in both animal models and humans indicate that
recruitment of prefrontal inhibitory control of drug seeking is still functional
after prolonged cocaine use. Preclinical investigation of the mechanisms
underlying this capacity may contribute to designing new behavioral and/or
pharmacologic strategies to promote its use for the prevention of relapse in
Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All
PMID: 22985696 [Indexed for MEDLINE]