title: Neuroleptics Affect Neuropeptide S and NPSR mRNA Levels in the Rat Brain.
abstract: Neuropeptide S (NPS) has a multidirectional regulatory activity, especially when considered as a potent endogenous anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signaling in various brain structures. However, there is no information regarding the influence of treatment with antipsychotics on brain NPS expression. In the current study, we assessed the NPS and NPS receptor (NPSR) mRNA levels in the brains of rats shortly and chronically treated with chlorpromazine and olanzapine using quantitative real-time PCR. Both single-dose and long-term (4 months) olanzapine treatment led to the upregulation of NPS expression in the rat hypothalamus. It supports the hypothesis that NPS is involved in the dopamine-dependent anxiolytic actions of selected neuroleptics and possibly also in the pathophysiology of mental disorders. On the other hand, NPSR expression decreased after single-dose and chronic chlorpromazine administration in the hypothalamus, as well as after chronic olanzapine and chlorpromazine administration in the striatum and hippocampus. These results cast a new light on the pharmacology of antipsychotics and contribute to a better understanding of the mechanisms responsible for their action. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Medyków Street 18, Katowice, 40-752, Poland. apalasz@sum.edu.pl.
authors.forename: Artur
authors.initials: A
authors.lastname: Pałasz
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Medyków Street 18, Katowice, 40-752, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rojczyk
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002746:Chlorpromazine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D000077152:Olanzapine; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011954:Receptors, Dopamine / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D009479:Neuropeptides; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D018013:Receptors, Neuropeptide; C568280:neuropeptide S receptor, rat; C534458:neuropeptide S, rat; D001569:Benzodiazepines; D000077152:Olanzapine; D002746:Chlorpromazine; D004298:Dopamine
keywords: Chlorpromazine; NPSR; Neuroleptics; Neuropeptide S; Olanzapine