Long-term effects of newer antipsychotic drugs on neuronal nitric oxide synthase in rat brain.
Neuronal nitric oxide synthase (nNOS) catalyzes the synthesis of neuronal nitric oxide from L-arginine. Behavioral and neurochemical studies implicate neuronal nitric oxide in the pathophysiology of schizophrenia and in the actions of standard antipsychotic drugs. However, involvement of nNOS in the actions of newer antipsychotic drugs requires further investigation. Accordingly, density levels of nNOS, a marker for neuronal nitric oxide production, were examined in rat forebrain regions by computed autoradiography after repeated treatment (28 days) with three newer antipsychotic agents, olanzapine, risperidone, and quetiapine. No significant differences in nNOS levels were detected in representative cortical, limbic, and extrapyramidal brain regions of drug-treated vs vehicle-treated animals. The findings suggest that nNOS plays a minimal role in mediating the long-term actions of newer antipsychotic drugs.
Tarazi
Frank I
FI
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, MA 02478, USA. ftarazi@hms.harvard.edu
Zhang
Kehong
K
Baldessarini
Ross J
RJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D003987:Dibenzothiazepines / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D014316:Tritium; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D018967:Risperidone; D000077152:Olanzapine