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

Abstract

AbstractDysfunction of subcortical D2-like dopamine receptors (D2Rs) can lead to positive symptoms of schizophrenia, and their analog, the increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D2Rs. The D2R 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 VP D2Rs. We hypothesize that the microinjection of sulpiride into the VP can normalize hyperactivity in MAM-E17 rats. In addition, recently, we showed that the microinjection of sulpirid into the VP induces place preference in neurotypical rats. Thus, we aimed to test whether intra-VP sulpiride can also have a rewarding effect in MAM-E17 rats. Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical (SAL-E17) and MAM-E17 schizophrenia model rats to test locomotor activity and the potential locomotor-reducing and rewarding effects of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, and the controls received only vehicle. The results of the present study demonstrated that the increased locomotor activity of the MAM-E17 rats was caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analog habituation disturbance of the MAM-E17 animals. Furthermore, we showed that the largest dose of sulpiride administered into the VP induced CPP in the SAL-E17 animals but not in the MAM-E17 animals. These findings revealed that VP D2Rs play an important role in the formation of positive symptom-like habituation disturbances in MAM-E17 rats.