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One of the obstacles to the study of drug dependence is the question of whether animals experience true addiction, rather than simply self-administering drugs. Two recently published papers in Science present evidence for a transition from drug taking to compulsive drug-seeking behaviour in rats — which parallels compulsive behaviour in humans — and help to explain the conditions under which this occurs.
Vanderschuren and Everitt reported that in rats trained to self-administer cocaine, there was a transition from casual drug taking to the compulsive drug seeking that is characteristic of addictive behaviour. They showed that the presentation of a conditioned harmful stimulus (the delivery of an electric shock) curbed drug-seeking behaviour in rats with a short-lived exposure to cocaine but had no effect in rats that had experienced a prolonged access to the drug. This effect was not seen when a natural reinforcer, sucrose, was used in place of the drug. Moreover, further experiments showed that an increase in incentive value of the drug and reduced fear conditioning or pain sensitivity could not explain these changes in behaviour. So, extended drug experience seems to induce compulsive, addiction-like behaviour. Deroche-Gamonet et al. showed a similar transition to compulsive behaviour in rats after prolonged access to cocaine, again evident from an increase in drug seeking when the drug was not available and persistent drug taking in the face of harmful consequences (shock conditioning). Furthermore, these authors reported high levels of activity motivated towards procuring the drug. This was measured using a 'progressive-ratio schedule', whereby the number of responses required to receive the drug progressively increases until the animal reaches 'breaking point' (the maximum amount of work that an animal is prepared to do to receive the reward); the dependent rats showed higher breaking points. These three symptoms were present only in a subset (17%) of the rats — similar to the percentage of human cocaine users that are diagnosed as addicts — whereas the remainder tended to show a decrease in these addiction-like behaviours over time, despite no differences in cocaine intake during the self-administration period. Importantly, a high level of drug-seeking behaviour was associated with relapse after periods of withdrawal of either 5 days or 30 days, which was not seen in rats that showed low levels of addiction-like behaviour. These two papers present an animal model that distinguishes between drug taking and true addiction, and so opens up new avenues for the study of the biological mechanisms of drug dependence. Crucially, this might help to answer some key questions, such as why some individuals are more vulnerable to addiction than other.

Publicado en prestigiosa revista cientifica el October 2004 Vol 5 No 10