The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats

The malfunction of subcortical D2-like dopamine receptors (D 2 Rs) can lead to positive symptoms of schizophrenia and the analogue increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D 2 Rs. The D 2 R antagonist sulpiride is a widespread antipsychotic drug, which can alleviate positive symptoms in human patients. However, it is still not known how sulpiride can influence positive symptoms via the VP D 2 Rs. We hypothesize that the sulpiride microinjected into the VP can normalize hyperactivity of MAM-E17 rats. In addition, recently, we have shown that the sulpirid microinjected into the VP induces place preference in neurotypical rats. Thus, we aim to test whether intra-VP sulpiride can have a rewarding effect in MAM-E17 rats as well. Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical and MAM-E17 schizophrenia model rats to test their locomotor activity and the potential locomotor-reducing and rewarding effect of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, controls received only vehicle. Results of present experiments demonstrate that the increased locomotor activity of the MAM-E17 rats is in fact caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analogue habituation disturbance of the MAM-E17 animals. Furthermore, we show that the largest dose of sulpiride administered into the VP induces CPP in neurotypical, but not in MAM-E17 animals. These findings reveal that the VP D 2 Rs play an important role in the formation of the positive symptom-like habituation disturbance of MAM-E17 rats.