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A therapeutic approach focusing on the conditional effects of drugs





Hedonic and reinforcing properties of drugs of abuse are associated with the brain dopaminergic system. All drugs increase dopa~mine in the shell of nucleus accumbens, a brain region which express the D`indiceb1`/indiceb (D`indiceb1`/indicebR) and D`indiceb3`/indiceb (D`indiceb3`/indicebR) dopamine receptors. Converging pharmacological, human post-mortem and genetic studies suggest the involvement of the D`indiceb3`/indicebR in reinforcing effects of drugs. The D`indiceb3`/indicebR is also implicated in the behavioral sensitization process. These data suggest the use of D`indiceb3`/indicebR agonists as partial substitutes to treat cocaine-dependence, by affecting its reward component. However, substitution therapies maintain dependence and may be inefficient on drug craving and relapse, which are the unsolved and critical problems in the treatment of drug addiction. Recently, a highly selective and partial D`indiceb3`/indicebR agonist, BP 897, was shown to reduce cocaine-associated cue~controlled behaviour in rats, without having any primary intrinsic effects. As drug-associated cues maintain drug-seeking in animals and elicit craving and relapse in humans, such D`indiceb3`/indicebR agents have potential therapeutic applications.

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