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.

Effect of long-term treatment with classical neuroleptics on NPQ/spexin, kisspeptin and POMC mRNA expression in the male rat amygdala

“…The differences observed in studied drugs are most likely a consequence of different modes of their action at the molecular level Hypothetically, an increase of SPX expression after neuroleptic treatment may be associated with the decreased level of anxiety in rats, but this possibility has to be examined in further behavioural studies. Remarkably, the high increase of SPX mRNA level after chronic chlorpromazine administration seems to be analogical to previous data showing that expression of neuropeptide S (NPS) mRNA in the hypothalamus of rats treated with olanzapine was also elevated (Palasz and Rojczyk 2015). Chlorpromazine as well as haloperidol gives rise to increased POMC expression, with seven-times higher modulation by haloperidol than chlorpromazine.…”

Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

“…The statistically significant elevation of the brainstem NPS mRNA level, after long-term haloperidol administration stays in agreement with our recent results showing that short and chronical treatment with the neuroleptics chlorpromazine and olanzapine increased the NPS mRNA expression in the rat hypothalamus (41). In addition, haloperidol stimulates the secretion of GnRH (34) and increases corticotrophin-releasing hormone (CRF) mRNA expression in the rat hypothalamus (42).…”

“…This result is consistent with our recent finding that NPSR mRNA levels in the same structures were decreased after chronical chlorpromazine and olanzapine administration. Additionally, both short and long-term exposition to chlorpromazine decreased the NPS mRNA level in the hypothalamus (41). Presented phenomena are rather difficult to interpret without specific analysis of potential interactions between NPSR mode of action and dopaminergic signalling.…”

Pharmacology, Physiology and Genetics of the Neuropeptide S System

“…For example, increased NPS release upon stress exposure has been detected in the rat amygdala by microdialysis, demonstrating that it is a functional neurotransmitter [ 29 ]. Regulation of NPS transcripts has been observed in rat brain after sleep deprivation [ 30 ] or treatment with neuroleptics [ 31 , 32 ].…”

“…NPSR1 mRNA expression is found in many areas of the rodent brain, with highest densities in several cortical structures, thalamic nuclei, hypothalamus, subiculum, and amygdala [ 3 , 26 , 27 ]. Neuroleptics and chronic morphine also appear to regulate NPSR1 mRNA in certain areas of the rat brain [ 31 , 32 , 33 ].…”