DIFFERENTIAL EFFECT OF ANTIPSYCHOTICS ON PLACE NAVIGATION OF RATS IN THE MORRIS WATER MAZE - A COMPARATIVE-STUDY BETWEEN NOVEL AND REFERENCE ANTIPSYCHOTICS

A group of novel neuroleptics (e.g. olanzapine, seroquel, sertindole a nd ziprasidone) and already marketed compounds (e.g. clozapine, halope ridol and risperidone) were tested for acute effect on spatial learnin g and memory in Morris' water maze task. Young rats were trained for 4 consecutive days (three trials/day) to find a platform situated benea th the water surface. Two compounds, sertindole and seroquel, were wit hout effect on spatial performance, whereas clozapine impaired perform ance on the first 2 test days but showed no effect compared to the con trols on the last 2 test days. Ziprasidone and olanzapine markedly imp aired spatial memory without affecting motor function (measured by the swimming speed). Risperidone and haloperidol also impaired performanc e but in addition both compounds significantly lowered the swimming sp eed. The present study indicates that several of the compounds impair spatial learning in Morris water maze. This might be of clinical impor tance in the treatment of schizophrenics, as many of these patients al ready show severe cognitive deficits. Therefore, certain antipsychotic s could worsen the preexisting memory deficits in schizophrenic patien ts and this aspect should be considered before antipsychotic treatment .