Effects of antipsychotic drugs on cholecystokinin and preprotachykinin (substance P) mRNA expression in the rat hippocampal formation

To assess the involvement of substance P (SP) and cholecystokinin (CCK) in the effects of antipsychotic drugs, preprotachykinin-A (PPT-A) and CCK mRNA expression was studied in the hippocampal formation using in situ hybridis ation following 21 daily i.p. injections with the typical antipsychotic dru g haloperidol(1 mg/kg) and the atypical drug clozapine (15 mg/kg). PPT-A mR NA levels were increased in the hippocampal CA3 subregion and in the entorh inal cortex after haloperidol, whereas a decrease was observed in the CA1 a fter clozapine. CCK mRNA levels increased in the CAI, the entorhinal cortex and in hilus, following both haloperidol and clozapine. It is suggested th at earlier findings of increased SP levels in the hippocampal Formation of schizophrenics may be a consequence of haloperidol treatment and that reduc ed hippocampal CCK and CCK mRNA levels found earlier in schizophrenics do n ot result from antipsychotic drug treatment. These results are consonant to the hypothesis that increased cortical CCK transmission may be beneficial in the treatment of psychosis. (C) 2000 Elsevier Science B.V. All rights re served.