Preclinical validation of a novel cocaine exposure therapy for relapse prevention.
Biological Psychiatry. 2011-09-01; 70(6): 593-598
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1. Biol Psychiatry. 2011 Sep 15;70(6):593-8. doi: 10.1016/j.biopsych.2011.03.036.
Epub 2011 May 14.
Preclinical validation of a novel cocaine exposure therapy for relapse
Mihindou C(1), Vouillac C, Koob GF, Ahmed SH.
(1)Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux,
BACKGROUND: Cocaine not only induces intense rewarding sensations but also
craving for more cocaine, particularly during abstinence, an effect that
contributes, together with other factors, to relapse. Here we sought to prevent
this effect by extinguishing the conditioned interoceptive cues of cocaine that
are thought to be acquired during repeated cocaine use.
METHODS: Cocaine-induced craving was studied in rats using the well-validated
model of drug-primed reinstatement of cocaine seeking. To extinguish the
conditioned interoceptive effects of cocaine, rats received daily repeated
cocaine priming in the absence of drug reinforcement.
RESULTS: Cocaine-primed reinstatement of cocaine seeking dramatically decreased
with repeated cocaine priming regardless of the testing dose and even following a
history of extended access to cocaine self-administration. The extinction of
cocaine-primed reinstatement of cocaine seeking was enduring, generalized to
stress-another major trigger of drug craving and relapse-and was
CONCLUSIONS: These findings clearly show that it is feasible to prevent the
ability of cocaine and stress to induce cocaine seeking using an approach
designed to extinguish the drug’s conditioned interoceptive cues. Although this
preclinical extinction approach has limitations that need to be overcome in
future research (i.e., its context-dependency), it may nevertheless represent a
promising basis for the development of a novel exposure therapy against cocaine
Copyright © 2011 Society of Biological Psychiatry. All rights reserved.
PMID: 21571256 [Indexed for MEDLINE]