Les effets d’un traitement chronique aux antipsychotiques sur la poursuite d’une récompense conditionnée
Substance abuse problems are excessively common in schizophrenia. Chronic antipsychotic treatment might be involved in this co-morbidity by inducing supersensitivity in the brain’s dopamine system. We have shown previously in the rat that continuous (via osmotic subcutaneous minipump), but not intermittent (via daily subcutaneous injection), treatment with haloperidol potentiates the ability of amphetamine to enhance the pursuit of a conditioned reward. Here, we assessed the effects of the atypical antipsychotic olanzapine. Continuous treatment with haloperidol, but not with olanzapine, enhanced the capacity of amphetamine to potentiate the pursuit of a conditioned reward (a light-tone stimulus previously paired with water). In addition, continuous haloperidol treatment augmented both amphetamine-induced locomotion and striatal c-fos mRNA expression. These effects were either absent or less pronounced following continuous olanzapine treatment. Thus, continuous treatment with a typical, but not with an atypical, antipsychotic enhanced the incentive motivational properties of a reward cue, and this was potentially linked to the development of behavioural supersensitivity to amphetamine and to a greater ability of amphetamine to engage the caudate-putamen. Thus, a typical antipsychotic like haloperidol appears to modify the brain’s reward system in ways that could contribute to drug-seeking and drug-taking behaviour, but an atypical antipsychotic like olanzapine might be less likely to do so. We suggest that atypical antipsychotics might be a preferential option in schizophrenic patients at risk for drug abuse or addiction.
Antipsychotics Typical Atypical Conditioned reward Dopamine supersensitivity Immediate early gene Caudate-putamen