Increased Novelty-induced Motor Activity and Reduced Depression-like Behavior in Neuropeptide Y (NPY)-Y4 Receptor Knockout Mice

Overview

Journal Neuroscience

Specialty Neurology

Date 2009 Jan 6

PMID 19121371

Citations 30

Authors

R O Tasan

S Lin

A Hetzenauer

N Singewald

H Herzog

G Sperk

Affiliations

Soon will be listed here.

Abstract

There is growing evidence that neuropeptide Y (NPY) acting through Y1 and Y2 receptors has a prominent role in modulating anxiety- and depression-like behavior in rodents. However, a role of other Y-receptors like that of Y4 receptors in this process is poorly understood. We now investigated male Y2, Y4 single and Y2/Y4 double knockout mice in behavioral paradigms for changes in motor activity, anxiety and depression-like behavior. Motor activity was increased in Y2, Y4 and Y2/Y4 knockout mice under changing and stressful conditions, but not altered in a familiar environment. Y4 and Y2 knockout mice revealed an anxiolytic phenotype in the light/dark test, marble burying test and in stress-induced hyperthermia, and reduced depression-like behavior in the forced swim and tail suspension tests. In Y2/Y4 double knockout mice, the response in the light/dark test and in the forced swim test was further enhanced compared with Y4 and Y2 knockout mice, respectively. High levels of Y4 binding sites were observed in brain stem nuclei including nucleus of solitary tract and area postrema. Lower levels were found in the medial amygdala and hypothalamus. Peripheral administration of pancreatic polypeptide (PP) induced Y4 receptor-dependent c-Fos expression in brain stem, hypothalamus and amygdala. PP released peripherally from the pancreas in response to food intake, may act not only as a satiety signal but also modulate anxiety-related locomotion.

Citing Articles

Illuminating Neuropeptide Y Y Receptor Binding: Fluorescent Cyclic Peptides with Subnanomolar Binding Affinity as Novel Molecular Tools.

Gleixner J, Kopanchuk S, Gratz L, Tahk M, Laasfeld T, Veiksina S ACS Pharmacol Transl Sci. 2024; 7(4):1142-1168.

PMID: 38633582 PMC: 11019746. DOI: 10.1021/acsptsci.4c00013.

Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: A postmortem study.

Sharma A, Ren X, Zhang H, Pandey G Prog Neuropsychopharmacol Biol Psychiatry. 2021; 112:110428.

PMID: 34411658 PMC: 8489679. DOI: 10.1016/j.pnpbp.2021.110428.

Effects of Laboratory Housing Conditions on Core Temperature and Locomotor Activity in Mice.

Russell L, Hyatt W, Gannon B, Simecka C, Randolph M, Fantegrossi W J Am Assoc Lab Anim Sci. 2021; 60(3):272-280.

PMID: 33888181 PMC: 8145121. DOI: 10.30802/AALAS-JAALAS-20-000093.

Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines.

Chavez-Castillo M, Nunez V, Nava M, Ortega A, Rojas M, Bermudez V Adv Pharmacol Sci. 2019; 2019:7943481.

PMID: 30719038 PMC: 6335777. DOI: 10.1155/2019/7943481.

A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive-compulsive disorder: Mapping the way forward.

Brouwer G, Fick A, Harvey B, Wolmarans D Cogn Affect Behav Neurosci. 2018; 19(1):1-39.

PMID: 30361863 DOI: 10.3758/s13415-018-00653-4.

References

Steru L, Chermat R, Thierry B, Simon P . The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985; 85(3):367-70. DOI: 10.1007/BF00428203. View

Saha S, Batten T, Henderson Z . A GABAergic projection from the central nucleus of the amygdala to the nucleus of the solitary tract: a combined anterograde tracing and electron microscopic immunohistochemical study. Neuroscience. 2000; 99(4):613-26. DOI: 10.1016/s0306-4522(00)00240-2. View

Parker S, Balasubramaniam A . Neuropeptide Y Y2 receptor in health and disease. Br J Pharmacol. 2007; 153(3):420-31. PMC: 2241788. DOI: 10.1038/sj.bjp.0707445. View

Cryan J, Markou A, Lucki I . Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002; 23(5):238-45. DOI: 10.1016/s0165-6147(02)02017-5. View

Greber S, Schwarzer C, Sperk G . Neuropeptide Y inhibits potassium-stimulated glutamate release through Y2 receptors in rat hippocampal slices in vitro. Br J Pharmacol. 1994; 113(3):737-40. PMC: 1510458. DOI: 10.1111/j.1476-5381.1994.tb17055.x. View

Freitag C, Svendsen A, Feldthus N, Lossl K, Sheikh S . Coupling of the human Y2 receptor for neuropeptide Y and peptide YY to guanine nucleotide inhibitory proteins in permeabilized SMS-KAN cells. J Neurochem. 1995; 64(2):643-50. DOI: 10.1046/j.1471-4159.1995.64020643.x. View

Singewald N, Sharp T . Neuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos immunocytochemistry. Neuroscience. 2000; 98(4):759-70. DOI: 10.1016/s0306-4522(00)00177-9. View

Lister R . The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 1987; 92(2):180-5. DOI: 10.1007/BF00177912. View

Lucki I . The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol. 1998; 8(6-7):523-32. DOI: 10.1097/00008877-199711000-00010. View

10.

Yan H, Yang J, Marasco J, Yamaguchi K, Brenner S, Collins F . Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors. Proc Natl Acad Sci U S A. 1996; 93(10):4661-5. PMC: 39335. DOI: 10.1073/pnas.93.10.4661. View

11.

Silva J, Larsen P . Adrenergic activation of triiodothyronine production in brown adipose tissue. Nature. 1983; 305(5936):712-3. DOI: 10.1038/305712a0. View

12.

Kask A, Harro J, von Horsten S, Redrobe J, Dumont Y, Quirion R . The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y. Neurosci Biobehav Rev. 2002; 26(3):259-83. DOI: 10.1016/s0149-7634(01)00066-5. View

13.

Chen X, DiMaggio D, Han S, Westfall T . Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y2 receptors. Am J Physiol. 1997; 273(4):H1737-44. DOI: 10.1152/ajpheart.1997.273.4.H1737. View

14.

Xu Y, Reinscheid R, Huitron-Resendiz S, Clark S, Wang Z, Lin S . Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron. 2004; 43(4):487-97. DOI: 10.1016/j.neuron.2004.08.005. View

15.

Painsipp E, Wultsch T, Edelsbrunner M, Tasan R, Singewald N, Herzog H . Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice. Genes Brain Behav. 2008; 7(5):532-42. PMC: 4359911. DOI: 10.1111/j.1601-183X.2008.00389.x. View

16.

Dumont Y, Moyse E, Fournier A, Quirion R . Distribution of peripherally injected peptide YY ([125I] PYY (3-36)) and pancreatic polypeptide ([125I] hPP) in the CNS: enrichment in the area postrema. J Mol Neurosci. 2007; 33(3):294-304. DOI: 10.1007/s12031-007-9007-9. View

17.

Michel M, Beck-Sickinger A, Cox H, Doods H, Herzog H, Larhammar D . XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev. 1998; 50(1):143-50. View

18.

Redrobe J, Dumont Y, Herzog H, Quirion R . Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from Y2 receptor knockout mice. Behav Brain Res. 2003; 141(2):251-5. DOI: 10.1016/s0166-4328(02)00374-1. View

19.

Ueno N, Asakawa A, Satoh Y, Inui A . Increased circulating cholecystokinin contributes to anorexia and anxiety behavior in mice overexpressing pancreatic polypeptide. Regul Pept. 2007; 141(1-3):8-11. DOI: 10.1016/j.regpep.2006.12.019. View

20.

Bourin M, Hascoet M . The mouse light/dark box test. Eur J Pharmacol. 2003; 463(1-3):55-65. DOI: 10.1016/s0014-2999(03)01274-3. View