Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction.
Neuroscience & Biobehavioral Reviews. 2010-11-01; 35(2): 172-184
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1. Neurosci Biobehav Rev. 2010 Nov;35(2):172-84. doi:
10.1016/j.neubiorev.2010.04.005. Epub 2010 Apr 22.
Validation crisis in animal models of drug addiction: beyond non-disordered drug
use toward drug addiction.
(1)Université Bordeaux 2, CNRS, Mouvement Adaptation Cognition, UMR 5227, France.
In standard drug self-administration settings, animals have no choice than drug
use. As a result, serious doubt exists about the interpretation of drug use in
experimental animals. Is it symptomatic of an underlying addiction state or
merely an expectable response to lack of choice? This incertitude in turn casts a
shadow over many behavioral and neurobiological changes that have been well
documented in animals following extended drug self-administration. Do they
reflect pathological dysfunctions or normal neurobiological adaptations? Here I
address these questions by focusing on intravenous cocaine self-administration in
the rat as a paradigm example. Overall, available evidence shows that when a
valuable behavioral option, even a biologically or physiologically inessential
one, is made available during access to cocaine self-administration, most rats
readily abstain from cocaine use in favor of the alternative reward regardless of
the amount of past cocaine use. Only a small minority of rats continue to
self-administer the drug despite the opportunity of making a different choice.
This pattern of results (i.e., abstinence in most rats; cocaine preference in few
rats) maps well onto what is currently known about the epidemiology of human
cocaine addiction. It is thus possible that the minority of cocaine-preferring
rats would be homologous to the minority of human cocaine users with a diagnosis
of addiction while the remaining majority of abstinent rats would be resilient to
cocaine addiction. Choice could represent an objective method of selection of
addicted animals for future research on the neurobiological dysfunctions that are
hypothesized to underlie cocaine addiction. Other competing interpretations of
the same pattern of results are also discussed at the end of this review.
Copyright © 2010 Elsevier Ltd. All rights reserved.
PMID: 20417231 [Indexed for MEDLINE]