Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-26T03:36:00.832Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  15 October 2015

Artur Palasz ,
Ewa Rojczyk ,
Milosz Golyszny ,
Lukasz Filipczyk ,
John J. Worthington  and
Ryszard Wiaderkiewicz
Artur Palasz*
Affiliation:
Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
Ewa Rojczyk
Affiliation:
Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
Milosz Golyszny
Affiliation:
Student Scientific Society, Medical University of Silesia, Katowice, Poland
Lukasz Filipczyk
Affiliation:
Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
John J. Worthington
Affiliation:
Manchester Immunology Group, University of Manchester, Manchester, UK
Ryszard Wiaderkiewicz
Affiliation:
Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
*
Artur Palasz, Department of Histology, School of Medicine in Katowice, Medical University of Silesia, 18 Medykow Street, 40-752 Katowice, Poland. Tel: +48 32 2088363; Fax: +48 32 2526574; E-mail: apalasz@sum.edu.pl
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression.

Methods

We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction.

Results

Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum.

Conclusions

This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

Keywords

brainstemhaloperidolneurolepticsneuropeptide sNPSR
Type
Short Communications
Information
Acta Neuropsychiatrica , Volume 28 , Issue 2 , April 2016 , pp. 110 - 116
Check for updates
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Pape, HC, Jungling, K, Seidenbecher, T, Lesting, J, Reinscheid, RK. Neuropeptide S: a transmitter system in the brain regulating fear and anxiety. Neuropharmacology 2010;58:29–34.CrossRefGoogle Scholar
2. Beck, B, Fernette, B, Stricker-Krongrad, A. Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. Biochem Biophys Res Commun 2005;332:859–865.CrossRefGoogle ScholarPubMed
3. Cannella, N, Kallupi, M, Ruggeri, B, Ciccocioppo, R, Ubaldi, M. The role of the neuropeptide S system in addiction: focus on its interaction with the CRF and hypocretin/orexin neurotransmission. Prog Neurobiol 2013;100:48–59.CrossRefGoogle ScholarPubMed
4. Chauveau, F, Lange, MD, Jungling, K, Lesting, J, Seidenbecher, T, Pape, HC. Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala. Neuropsychopharmacology 2012;37:1588–1599.CrossRefGoogle ScholarPubMed
5. Kumsta, R, Chen, FS, Pape, HC, Heinrichs, M. Neuropeptide S receptor gene is associated with cortisol responses to social stress in humans. Biol Psychol 2013;93:304–307.CrossRefGoogle ScholarPubMed
6. Oishi, M, Kushikata, T, Niwa, H et al. Endogenous neuropeptide S tone influences sleep-wake rhythm in rats. Neurosci Lett 2014;581:94–97.CrossRefGoogle ScholarPubMed
7. Pulga, A, Ruzza, C, Rizzi, A, Guerrini, R, Calo, G. Anxiolytic- and panicolytic-like effects of Neuropeptide S in the mouse elevated T-maze. Eur J Neurosci 2012;36:3531–3537.CrossRefGoogle ScholarPubMed
8. Slattery, DA, Naik, RR, Grund, T et al. Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity. J Neurosci 2015;35:4599–4613.CrossRefGoogle ScholarPubMed
9. Clark, SD, Duangdao, DM, Schulz, S et al. Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry. J Comp Neurol 2011;519:1867–1893.CrossRefGoogle ScholarPubMed
10. Xu, YL, Gall, CM, Jackson, VR, Civelli, O, Reinscheid, RK. Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 2007;500:84–102.CrossRefGoogle ScholarPubMed
11. Guerrini, R, Salvadori, S, Rizzi, A, Regoli, D, Calo, G. Neurobiology, pharmacology, and medicinal chemistry of neuropeptide S and its receptor. Med Res Rev 2010;30:751–777.CrossRefGoogle ScholarPubMed
12. Wegener, G, Finger, BC, Elfving, B et al. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression. Int J Neuropsychopharmacol 2012;15:375–387.CrossRefGoogle Scholar
13. Lukas, M, Neumann, ID. Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: social versus non-social effects. Neuropharmacology 2012;62:398–405.CrossRefGoogle ScholarPubMed
14. Si, W, Aluisio, L, Okamura, N et al. Neuropeptide S stimulates dopaminergic neurotransmission in the medial prefrontal cortex. J Neurochem 2010;115:475–482.CrossRefGoogle ScholarPubMed
15. Dine, J, Ionescu, IA, Stepan, J et al. Identification of a role for the ventral hippocampus in neuropeptide S-elicited anxiolysis. PLoS One 2013;8:e60219.CrossRefGoogle ScholarPubMed
16. Jungling, K, Seidenbecher, T, Sosulina, L et al. Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala. Neuron 2008;59:298–310.CrossRefGoogle ScholarPubMed
17. Ruland, T, Domschke, K, Schutte, V et al. Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic. Eur Neuropsychopharmacol 2015; pii:S0924-977X(15)00229-1, doi:10.1016/j.euroneuro.2015.07.011.CrossRefGoogle ScholarPubMed
18. Zhang, S, Jin, X, You, Z et al. Persistent nociception induces anxiety-like behavior in rodents: role of endogenous neuropeptide S. Pain 2014;155:1504–1515.CrossRefGoogle ScholarPubMed
19. Lennertz, L, Quednow, BB, Schuhmacher, A et al. 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 2012;15:1205–1215.CrossRefGoogle ScholarPubMed
20. Garay, RP, Samalin, L, Hameg, A, Llorca, PM. Investigational drugs for anxiety in patients with schizophrenia. Expert Opin Investig Drugs 2015;24:507–517.CrossRefGoogle ScholarPubMed
21. Braga, RJ, Reynolds, GP, Siris, SG. Anxiety comorbidity in schizophrenia. Psychiatry Res 2013;210:1–7.CrossRefGoogle ScholarPubMed
22. Didonet, JJ, Cavalcante, JC, Souza Lde, S et al. Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice. Behav Brain Res 2014;266:29–36.CrossRefGoogle ScholarPubMed
23. Li, MS, Peng, YL, Jiang, JH et al. Neuropeptide S Increases locomotion activity through corticotropin-releasing factor receptor 1 in substantia nigra of mice. Peptides 2015;71:196–201.CrossRefGoogle ScholarPubMed
24. Gass, N, Schwarz, AJ, Sartorius, A et al. Haloperidol modulates midbrain-prefrontal functional connectivity in the rat brain. Eur Neuropsychopharmacol 2013;23:1310–1319.CrossRefGoogle ScholarPubMed
25. Cobos, EJ, Del Pozo, E, Baeyens, JM. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells. J Neurochem 2007;102:812–825.CrossRefGoogle ScholarPubMed
26. Roth, BL, Meltzer, HY, Khan, N. Binding of typical and atypical antipsychotic drugs to multiple neurotransmitter receptors. Adv Pharmacol 1998;42:482–485.CrossRefGoogle ScholarPubMed
27. Seeman, P, Tallerico, T.. Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry 1998;3:123–134.CrossRefGoogle ScholarPubMed
28. Budden, MG. A comparative study of haloperidol and diazepam in the treatment of anxiety. Curr Med Res Opin 1979;5:759–765.CrossRefGoogle ScholarPubMed
29. Leucht, S, Cipriani, A, Spineli, L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382:951–962.CrossRefGoogle ScholarPubMed
30. Stracina, T, Slaninova, I, Polanska, H et al. Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts. Tohoku J Exp Med 2015;236:199–207.CrossRefGoogle ScholarPubMed
31. Marx, CE, Shampine, LJ, Duncan, GE et al. Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy? Pharmacol Biochem Behav 2006;84:598–608.CrossRefGoogle ScholarPubMed
32. Millan, MJ, Brocco, M, Gobert, A, Schreiber, R, Dekeyne, A. S-16924 [(R)-2-[1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-ethyl]- pyrrolidin-3yl]-1-(4-fluorophenyl)-ethanone], a novel, potential antipsychotic with marked serotonin1A agonist properties: III. Anxiolytic actions in comparison with clozapine and haloperidol. J Pharmacol Exp Ther 1999;288:1002–1014.Google Scholar
33. Basta-Kaim, A, Budziszewska, B, Jaworska-Feil, L et al. Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases. Neuropsychopharmacology 2006;31:853–865.CrossRefGoogle ScholarPubMed
34. Umathe, SN, Wanjari, MM, Manna, SS, Jain, NS. A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol. Neuropeptides 2009;43:251–257.CrossRefGoogle ScholarPubMed
35. Tringali, G, Lisi, L, De Simone, ML et al. Effects of olanzapine and quetiapine on corticotropin-releasing hormone release in the rat brai. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1017–1021.CrossRefGoogle Scholar
36. Gruber, SH, Nomikos, GG, Mathe, AA. Effects of haloperidol and risperidone on neurotensin levels in brain regions and neurotensin efflux in the ventral striatum of the rat. Neuropsychopharmacology 2002;26:595–604.CrossRefGoogle ScholarPubMed
37. Huang, XF, Deng, C, Zavitsanou, K, Neuropeptide, Y. mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats. Neuropeptides 2006;40:213–219.CrossRefGoogle ScholarPubMed
38. Kursungoz, C, Ak, M, Yanik, T. Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats. Brain Res 2015;1596:146–155.CrossRefGoogle ScholarPubMed
39. Ferno, J, Varela, L, Skrede, S et al. Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLoS One 2011;6:e20571.CrossRefGoogle ScholarPubMed
40. Angelucci, F, Gruber, SH, Caltagirone, C, Mathe, AA. Differential effects of olanzapine, haloperidol and risperidone on calcitonin gene-related peptide in the rat brain. Neuropeptides 2008;42:535–541.CrossRefGoogle ScholarPubMed
41. Pałasz, A, Rojczyk, E. Neuroleptics affect neuropeptide S and NPSR mRNA levels in the rat brain. J Mol Neurosci 2015:1–6, doi:10.1007/s12031-015-0625-3 [epublished ahead of print].Google ScholarPubMed
42. Park, SW, Choi, SM, Lee, JG et al. Differential effects of ziprasidone and haloperidol on immobilization-stress-induced CRF mRNA expression in the hypothalamic paraventricular nucleus of rats. Neuropsychobiology 2011;63:29–34.CrossRefGoogle ScholarPubMed
43. Rojczyk, E, Palasz, A, Wiaderkiewicz, R. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus. Neuropeptides 2015;51:31–42.CrossRefGoogle Scholar
44. Castro, AA, Moretti, M, Casagrande, TS et al. Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: a comparative study with amphetamine and diazepam. Pharmacol Biochem Behav 2009;91:636–642.CrossRefGoogle Scholar
45. Rasmussen, K, Hsu, MA, Yang, Y. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: implications for antipsychotic therapy. Neuropsychopharmacology 2007;32:786–792.CrossRefGoogle ScholarPubMed
46. White, FJ, Wang, RY. Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 1983;221:1054–1057.CrossRefGoogle ScholarPubMed
47. Stockton, ME, Rasmussen, K. Electrophysiological effects of olanzapine, a novel atypical antipsychotic, on A9 and A10 dopamine neurons. Neuropsychopharmacology 1996;14:97–105.CrossRefGoogle ScholarPubMed
48. Mochizuki, T, Kim, J, Sasaki, K. Microinjection of neuropeptide S into the rat ventral tegmental area induces hyperactivity and increases extracellular levels of dopamine metabolites in the nucleus accumbens shell. Peptides 2010;31:926–931.CrossRefGoogle ScholarPubMed
49. Barbaccia, ML, Affricano, D, Purdy, RH, Maciocco, E, SPIGA, F, Biggio, G. Clozapine, but not haloperidol, increases brain concentrations of neuroactive steroids in the rat. Neuropsychopharmacology 2001;25:489–497.CrossRefGoogle Scholar
50. Mead, A, Li, M, Kapur, S. Clozapine and olanzapine exhibit an intrinsic anxiolytic property in two conditioned fear paradigms: contrast with haloperidol and chlordiazepoxide. Pharmacol Biochem Behav 2008;90:551–562.CrossRefGoogle ScholarPubMed