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.
References
Anedda F, Zucchelli M, Schepis D, Hellquist A, Corrado L, D’Alfonso S, Achour A, McInerney G, Bertorello A, Lordal M, Befrits R, Bjork J, Bresso F, Torkvist L, Halfvarson J, Kere J, D’Amato M (2011) Multiple polymorphisms affect expression and function of the neuropeptide S receptor (NPSR1). PLoS One 6:e29523
Angelucci F, Gruber SH, Caltagirone C, Mathe AA (2008) Differential effects of olanzapine, haloperidol and risperidone on calcitonin gene-related peptide in the rat brain. Neuropeptides 42:535–541
Basta-Kaim A, Budziszewska B, Jaworska-Feil L, Tetich M, Kubera M, Leskiewicz M, Otczyk M, Lason W (2006) Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells—an involvement of protein kinases. Neuropsychopharmacology 31:853–865
Beck B, Fernette B, Stricker-Krongrad A (2005) Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. Biochem Biophys Res Commun 332:859–865
Cannella N, Kallupi M, Ruggeri B, Ciccocioppo R, Ubaldi M (2013) The role of the neuropeptide S system in addiction: focus on its interaction with the CRF and hypocretin/orexin neurotransmission. Prog Neurobiol 100:48–59
Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R (2009) Persistent increase of alcohol-seeking evoked by neuropeptide S: an effect mediated by the hypothalamic hypocretin system. Neuropsychopharmacology 34:2125–2134
Castro AA, Moretti M, Casagrande TS, Martinello C, Petronilho F, Steckert AV, Guerrini R, Calo G, Dal Pizzol F, Quevedo J, Gavioli EC (2009) Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: a comparative study with amphetamine and diazepam. Pharmacol Biochem Behav 91:636–642
Chauveau F, Lange MD, Jungling K, Lesting J, Seidenbecher T, Pape HC (2012) Prevention of stress-impaired fear extinction through neuropeptide S action in the lateral amygdala. Neuropsychopharmacology 37:1588–1599
Clark SD, Duangdao DM, Schulz S, Zhang L, Liu X, Xu YL, Reinscheid RK (2011) Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry. J Comp Neurol 519:1867–1893
Cohrs S, Roher C, Jordan W, Meier A, Huether G, Wuttke W, Ruther E, Rodenbeck A (2006) The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects. Psychopharmacol (Berl) 185:11–18
Dannlowski U, Kugel H, Franke F, Stuhrmann A, Hohoff C, Zwanzger P, Lenzen T, Grotegerd D, Suslow T, Arolt V, Heindel W, Domschke K (2011) Neuropeptide-S (NPS) receptor genotype modulates basolateral amygdala responsiveness to aversive stimuli. Neuropsychopharmacol 36:1879–1885
Didonet JJ, Cavalcante JC, Souza Lde S, Costa MS, Andre E, Soares-Rachetti Vde P, Guerrini R, Calo G, Gavioli EC (2014) Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice. Behav Brain Res 266:29–36
Dine J, Ionescu IA, Stepan J, Yen YC, Holsboer F, Landgraf R, Eder M, Schmidt U (2013) Identification of a role for the ventral hippocampus in neuropeptide S-elicited anxiolysis. PLoS One 8:e60219
Domschke K, Reif A, Weber H, Richter J, Hohoff C, Ohrmann P, Pedersen A, Bauer J, Suslow T, Kugel H, Heindel W, Baumann C, Klauke B, Jacob C, Maier W, Fritze J, Bandelow B, Krakowitzky P, Rothermundt M, Erhardt A, Binder EB, Holsboer F, Gerlach AL, Kircher T, Lang T, Alpers GW, Strohle A, Fehm L, Gloster AT, Wittchen HU, Arolt V, Pauli P, Hamm A, Deckert J (2011) Neuropeptide S receptor gene—converging evidence for a role in panic disorder. Mol Psychiatry 16:938–948
Donner J, Haapakoski R, Ezer S, Melen E, Pirkola S, Gratacos M, Zucchelli M, Anedda F, Johansson LE, Soderhall C, Orsmark-Pietras C, Suvisaari J, Martin-Santos R, Torrens M, Silander K, Terwilliger JD, Wickman M, Pershagen G, Lonnqvist J, Peltonen L, Estivill X, D’Amato M, Kere J, Alenius H, Hovatta I (2010) Assessment of the neuropeptide S system in anxiety disorders. Biol Psychiatry 68:474–483
Duangdao DM, Clark SD, Okamura N, Reinscheid RK (2009) Behavioral phenotyping of neuropeptide S receptor knockout mice. Behav Brain Res 205:1–9
Ebner K, Rjabokon A, Pape HC, Singewald N (2011) Increased in vivo release of neuropeptide S in the amygdala of freely moving rats after local depolarisation and emotional stress. Amino Acids 41:991–996
Erdmann F, Kugler S, Blaesse P, Lange MD, Skryabin BV, Pape HC, Jungling K (2015) Neuronal expression of the human neuropeptide S receptor NPSR1 identifies NPS-induced calcium signaling pathways. PLoS One 10:e0117319
Fendt M, Imobersteg S, Burki H, McAllister KH, Sailer AW (2010) Intra-amygdala injections of neuropeptide S block fear-potentiated startle. Neurosci Lett 474:154–157
Gruber SH, Nomikos GG, Mathe AA (2002) Effects of haloperidol and risperidone on neurotensin levels in brain regions and neurotensin efflux in the ventral striatum of the rat. Neuropsychopharmacol 26:595–604
Guerrini R, Salvadori S, Rizzi A, Regoli D, Calo G (2010) Neurobiology, pharmacology, and medicinal chemistry of neuropeptide S and its receptor. Med Res Rev 30:751–777
Huang XF, Deng C, Zavitsanou K (2006) Neuropeptide Y mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats. Neuropeptides 40:213–219
Jungling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC (2008) Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 59:298–310
Kiss A, Bundzikova J, Pirnik Z, Mikkelsen JD (2010) Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry. J Neurosci Res 88:677–685
Kumsta R, Chen FS, Pape HC, Heinrichs M (2013) Neuropeptide S receptor gene is associated with Cortisol responses to social stress in humans. Biol Psychol 93:304–307
Lage R, Dieguez C, Lopez M (2006) Caffeine treatment regulates neuropeptide S system expression in the rat brain. Neurosci Lett 410:47–51
Lage R, Gonzalez CR, Dieguez C, Lopez M (2007) Nicotine treatment regulates neuropeptide system expression in the rat brain. Neurotoxicology 28:1129–1135
Laruelle M (2014) Schizophrenia: from dopaminergic to glutamatergic interventions. Curr Opin Pharmacol 14:97–102
Lennertz L, Quednow BB, Schuhmacher A, Petrovsky N, Frommann I, Schulze-Rauschenbach S, Landsberg MW, Steinbrecher A, Hofels S, Pukrop R, Klosterkotter J, Franke PE, Wolwer W, Gaebel W, Hafner H, Maier W, Wagner M, Mossner R (2012) The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response. Int J Neuropsychopharmacol 15:1205–1215
Liu X, Zeng J, Zhou A, Theodorsson E, Fahrenkrug J, Reinscheid RK (2011) Molecular fingerprint of neuropeptide S-producing neurons in the mouse brain. J Comp Neurol 519:1847–1866
Lukas M, Neumann ID (2012) Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: social versus non-social effects. Neuropharmacol 62:398–405
Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T (2008) Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform Nucleus. PLoS One 3:e2695
Oishi M, Kushikata T, Niwa H, Yakoshi C, Ogasawara C, Calo G, Guerrini R, Hirota K (2014) Endogenous neuropeptide S tone influences sleep-wake rhythm in rats. Neurosci Lett 581:94–97
Okamura N, Garau C, Duangdao DM, Clark SD, Jungling K, Pape HC, Reinscheid RK (2011) Neuropeptide S enhances memory during the consolidation phase and interacts with noradrenergic systems in the brain. Neuropsychopharmacol 36:744–752
Paneda C, Huitron-Resendiz S, Frago LM, Chowen JA, Picetti R, de Lecea L, Roberts AJ (2009) Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci 29:4155–4161
Pape HC, Jungling K, Seidenbecher T, Lesting J, Reinscheid RK (2010) Neuropeptide S: a transmitter system in the brain regulating fear and anxiety. Neuropharmacol 58:29–34
Park SW, Choi SM, Lee JG, Lee CH, Lee SJ, Kim NR, Kim YH (2011) Differential effects of ziprasidone and haloperidol on immobilization-stress-induced CRF mRNA expression in the hypothalamic paraventricular nucleus of rats. Neuropsychobiol 63:29–34
Pulga A, Ruzza C, Rizzi A, Guerrini R, Calo G (2012) Anxiolytic- and panicolytic-like effects of neuropeptide S in the mouse elevated T-maze. Eur J Neurosci 36:3531–3537
Rogoz Z (2013) Combined treatment with atypical antipsychotics and antidepressants in treatment-resistant depression: preclinical and clinical efficacy. Pharmacol Rep 65:1535–1544
Rojczyk E, Palasz A, Wiaderkiewicz R (2015) Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus. Neuropeptides 51:31–42
Shirayama Y, Ishima T, Oda Y, Okamura N, Iyo M, Hashimoto K (2015) Opposite roles for neuropeptide S in the nucleus accumbens and bed nucleus of the stria terminalis in learned helplessness rats. Behav Brain Res 291:67–71
Si W, Aluisio L, Okamura N, Clark SD, Fraser I, Sutton SW, Bonaventure P, Reinscheid RK (2010) Neuropeptide S stimulates dopaminergic neurotransmission in the medial prefrontal cortex. J Neurochem 115:475–482
Tringali G, Lisi L, De Simone ML, Aubry JM, Preziosi P, Pozzoli G, Navarra P (2009) Effects of olanzapine and quetiapine on corticotropin-releasing hormone release in the rat brain. Prog Neuropsychopharmacol Biol Psychiatry 33:1017–1021
Umathe SN, Wanjari MM, Manna SS, Jain NS (2009) A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol. Neuropeptides 43:251–257
Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (2007) Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 500:84–102
Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (2004) Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43:487–497
Zhang S, Jin X, You Z, Wang S, Lim G, Yang J, McCabe M, Li N, Marota J, Chen L, Mao J (2014) Persistent nociception induces anxiety-like behavior in rodents: role of endogenous neuropeptide S. Pain 155:1504–1515
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pałasz, A., Rojczyk, E. Neuroleptics Affect Neuropeptide S and NPSR mRNA Levels in the Rat Brain. J Mol Neurosci 57, 352–357 (2015). https://doi.org/10.1007/s12031-015-0625-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-015-0625-3