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 hybridisation following 21 daily i.p. injections with the typical antipsychotic drug haloperidol (1 mg/kg) and the atypical drug clozapine (15 mg/kg). PPT-A mRNA levels were increased in the hippocampal CA3 subregion and in the entorhinal cortex after haloperidol, whereas a decrease was observed in the CA1 after clozapine. CCK mRNA levels increased in the CA1, the entorhinal cortex and in hilus, following both haloperidol and clozapine. It is suggested that earlier findings of increased SP levels in the hippocampal formation of schizophrenics may be a consequence of haloperidol treatment and that reduced hippocampal CCK and CCK mRNA levels found earlier in schizophrenics do not 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.
Zachrisson
O
O
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, 171 76 Stockholm, Sweden. okz20@cam.ac.uk
Nomikos
G G
GG
Marcus
M M
MM
Svensson
T H
TH
Lindefors
N
N
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002766:Cholecystokinin / Q000235:genetics*; D003024:Clozapine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D014150:Antipsychotic Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D002766:Cholecystokinin; D003024:Clozapine; D006220:Haloperidol