title: Effects of neurotensin-2 receptor deletion on sensorimotor gating and locomotor activity.
abstract: Endogenous neurotensin (NT) has been implicated in brain processes relevant to schizophrenia as well as the therapeutic effects of antipsychotic drugs (APDs) used to treat this disorder. Converging evidence suggests that NT1 receptors mediate the antipsychotic-like effects of NT, such as prepulse inhibition (PPI) elevation. However, the role of NT2 receptors in these effects is not known. To investigate the contribution of NT2 receptors to the regulation of PPI, we measured baseline PPI and acoustic startle response (ASR), in male and female wild type (WT) and NT2 knockout (KO) mice. For comparison, we also measured locomotor activity. Baseline PPI was significantly elevated in both male (P<0.01) and female (P<0.01) NT2 KO compared to WT mice, while ASR was significantly decreased in KO mice of both genders (P<0.01). In contrast, female but not male KO mice exhibited significantly less baseline ambulations (P<0.05). These data support the regulation of baseline PPI, ASR and locomotor activity by endogenous NT acting at the NT2 receptor. Further studies investigating the role of NT2 receptors in the modulation of APD-like effects are warranted.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA. dfeifel@ucsd.edu
authors.forename: David
authors.initials: D
authors.lastname: Feifel
authors.forename: Zhen
authors.initials: Z
authors.lastname: Pang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Pang
authors.forename: Paul D
authors.initials: PD
authors.lastname: Shilling
authors.forename: Gilia
authors.initials: G
authors.lastname: Melendez
authors.forename: Rudy
authors.initials: R
authors.lastname: Schreiber
authors.forename: Donald
authors.initials: D
authors.lastname: Button
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009483:Neuropsychological Tests; D018028:Receptors, Neurotensin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013216:Reflex, Startle / Q000502:physiology*; D012727:Sex Characteristics
chemical_list: C490984:Ntsr2 protein, mouse; D018028:Receptors, Neurotensin
references.citation: J Mol Endocrinol. 2005 Jun;34(3):793-807
references.pmid: 15956348
references.citation: CNS Neurol Disord Drug Targets. 2006 Apr;5(2):205-18
references.pmid: 16611093
references.citation: Neuropsychopharmacology. 2004 Apr;29(4):731-8
references.pmid: 14760394
references.citation: Ann N Y Acad Sci. 1982;400:354-67
references.pmid: 6220630
references.citation: J Pharmacol Exp Ther. 2005 Feb;312(2):733-41
references.pmid: 15494551
references.citation: Psychopharmacology (Berl). 2004 Sep;175(3):353-9
references.pmid: 15107967
references.citation: Brain Res Dev Brain Res. 1999 Mar 12;113(1-2):115-31
references.pmid: 10064881
references.citation: Behav Neurosci. 2006 Oct;120(5):1093-102
references.pmid: 17014260
references.citation: Brain Res. 2010 Jan 13;1308:35-46
references.pmid: 19874804
references.citation: Biol Psychiatry. 2001 Dec 1;50(11):856-72
references.pmid: 11743941
references.citation: J Pharmacol Exp Ther. 1999 Feb;288(2):710-3
references.pmid: 9918579
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
references.pmid: 11549226
references.citation: Schizophr Bull. 1998;24(2):285-301
references.pmid: 9613626
references.citation: Neuropharmacology. 2010 Jan;58(1):173-8
references.pmid: 19596359
references.citation: J Pharmacol Exp Ther. 2005 Oct;315(1):256-64
references.pmid: 15987829
references.citation: Peptides. 2006 Oct;27(10):2476-87
references.pmid: 16919370
references.citation: J Comp Neurol. 2003 Jul 7;461(4):520-38
references.pmid: 12746866
references.citation: Expert Opin Investig Drugs. 2005 Apr;14(4):359-69
references.pmid: 15882113
references.citation: J Neurosci. 2001 Jan 15;21(2):601-8
references.pmid: 11160439
references.citation: J Neurochem. 2007 Sep;102(5):1669-1676
references.pmid: 17697051
references.citation: Neuropharmacology. 2010 Jun;58(8):1199-205
references.pmid: 20211191
references.citation: J Neurosci. 1998 Oct 15;18(20):8394-401
references.pmid: 9763482
references.citation: Behav Brain Res. 2003 Jul 14;143(1):7-14
references.pmid: 12842291
references.citation: Psychopharmacology (Berl). 1988;94(4):507-14
references.pmid: 3131796
references.citation: Neuropharmacology. 2010 Jun;58(7):1174-8
references.pmid: 20193696
references.citation: J Psychiatry Neurosci. 2006 Jul;31(4):229-45
references.pmid: 16862241
references.citation: CNS Drugs. 2007;21(1):13-23
references.pmid: 17190526
references.citation: Arch Gen Psychiatry. 1990 Feb;47(2):181-8
references.pmid: 2405807
references.citation: Behav Brain Res. 2007 Aug 6;181(2):278-86
references.pmid: 17559953
references.citation: Brain Res. 2004 Feb 13;998(1):122-9
references.pmid: 14725975
references.citation: Peptides. 2006 Oct;27(10):2469-75
references.pmid: 16872720