Review
Validation crisis in animal models of drug addiction: Beyond non-disordered drug use toward drug addiction

https://doi.org/10.1016/j.neubiorev.2010.04.005Get rights and content

Abstract

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.

Section snippets

Dependence or addiction: words of choice and choice of words

In current official diagnostic nomenclatures (e.g., 4th version of the American Psychiatric Association Diagnostic and Statistical Manual [DSM] of Mental Disorders), the term “dependence” is preferred to the word “addiction” to label the same behavioral disorder (see Section 1.3 below). However, several authors have recently called for a reversal of preference—a call that will be apparently followed in the forthcoming 5th version of the DSM (Miller and Holden, 2010). As put bluntly by O’Brien

Deconstruction of animal models of cocaine addiction

The goal of this section is to present a brief historical overview of scientific research on intravenous drug self-administration in experimental animals. This overview is not intended to be exhaustive or representative. Its goal is 2-fold: to praise the earlier researchers who have founded the field of animal drug self-administration and to reveal that since its birth, this field has regrettably largely neglected the role of choice in studying and analyzing cocaine addiction in experimental

Having the choice during access to cocaine self-administration

Previous research in rats has shown that concurrent access to a natural rewarding activity during access to cocaine can indeed influence cocaine self-administration (Campbell and Carroll, 2000, Ahmed, 2005). For instance, in a seminal series of experiments, Marilyn Carroll and colleagues showed that concurrent access to water sweetened with saccharin and glucose reduces the proportion of rats that eventually acquire cocaine self-administration and can also decrease the maintenance of cocaine

Choice as a sieve for cocaine addiction

Since the seminal work by Weeks, ample research has established that when no valuable options to drug use are available, most rats readily learn to self-administer cocaine and escalate cocaine intake following extended drug use (Ahmed, in press). In contrast, as shown here, when a valuable behavioral option, even a biologically or physiologically inessential one (i.e., for survival or reproduction), is made available during drug access, most rats readily abstain from cocaine use in favor of the

Acknowledgements

This work was supported by the French Research Council (CNRS), the Université Victor-Segalen Bordeaux 2, the National Research Agency (ANR), the Mission Interministerielle de Lutte contre les Drogues et la Toxicomanie (MILDT), the Conseil Regional d’Aquitaine and the Fondation pour la Recherche Médicale (FRM). The author thanks the present and past members of his research group for their dedication, commitment and effort. I also thank Dr. Sallouha Aidoudi for her comments on a previous version

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