Review article
Imbalance between drug and non-drug reward availability: A major risk factor for addiction

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Abstract

Laboratory animals self-administer most, though not all, drugs of abuse. Recent evidence shows that with increased drug availability, most laboratory rats develop all the major behavioral signs of addiction, including: 1) drug intake escalation, 2) increased motivation for the drug, 3) difficulty to abstain, 4) decreased reward function, and 5) inflexible drug use. The large prevalence of addicted rats may suggest that they are particularly vulnerable to develop compulsive drug use. I review evidence showing that this apparent vulnerability results in large part from the lack of positive (i.e., alternative non-drug rewards) and negative (i.e., costs) incentives capable of turning animals away from the pursuit of drugs. In particular, most animals seem to take drugs and eventually become addicted, not because drugs are intrinsically addictive, but more likely because drugs are the only significant sources of reward available in the laboratory. Laboratory animals would therefore represent more of a model of high-risk human groups than of the general population. Consequently, they should be more suited for searching factors that protect from, rather than predispose to, drug addiction. Reconsidering the environmental background of drug self-administration experiments in laboratory animals raises intriguing implications for understanding the initial demand for drug consumption and the transition to drug addiction, and for extrapolation from laboratory animals to humans.

Section snippets

Definition and behavioral criteria

Definitions of drug addiction have considerably evolved over the past 40 years, as illustrated by the multiple revisions of the Diagnostic and Statistical Manual (DSM) for Mental Disorders of the American Psychiatric Association (for interesting discussion, see Grant, 1989, Heather, 1998, Jaffe, 1992). Our views of drug addiction will probably continue to change with further clinical and experimental advances (Helmuth, 2003). Today, drug addiction or dependence (both terms are used

Drug availability as a major risk factor

Genetic, developmental and environmental factors are thought to contribute to the transition from drug use to drug addiction (Altman et al., 1996, Glantz and Pickens, 1992, Higgins et al., 2004, Koob and Le Moal, 2001, Uhl et al., 1995). Among environmental factors, drug availability represents a major risk factor. Increased drug availability can precipitate the transition to addiction, especially, as we will discuss later, when no or little non-drug rewards are concurrently available (Gawin

Neurobiological disruptions in the transition to compulsive drug use

Several different neurobiological mechanisms have been proposed to explain the transition from controlled to compulsive drug use in animals with extended access to the drug (Zernig et al., 2004 and associated commentaries). According to the hedonic allostasis hypothesis of drug addiction (Koob and Le Moal, 1997), which is a neurobiological elaboration on Solomon and Corbit's (1974) classical opponent–process theory of motivation, the precipitation of compulsive drug use would result from a

Origins of vulnerability to drug addiction in laboratory animals

We have shown that below a certain level of drug availability, most rats can repeatedly take cocaine without developing brain reward dysfunction and without showing signs of drug dependence. Above this level, however, the large majority of rats (about 70%) develop alterations in brain reward function that lead to compulsive drug use. This large prevalence of drug-addicted rats associated with increased drug availability seems excessive compared to current estimates in human drug users. Though

Summary

It is proposed that an environmental imbalance between drug and non-drug reward availability represents a major causative factor in drug addiction. The prevalence of drug addiction is expected to be high in environments that do not provide enough alternatives to drugs of abuse, such as in the environment of laboratory animals with extended access to drug self-administration, and low in environments that provide abundant non-drug reinforcers. Thus, reducing drug availability together with

Acknowledgments

The author was supported by grants from Université Victor-Segalen Bordeaux 2, CNRS, MILDT and Région Aquitaine. I thank George F. Koob for his intellectual support, Martine Cador, Valérie Daugé, Michel Le Moal, Guy Simonnet and Jean-Pol Tassin for critical discussions, and Mike Arends for research assistance.

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