Effects of neurotensin-2 receptor deletion on sensorimotor gating and locomotor activity.
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.
Feifel
David
D
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA. dfeifel@ucsd.edu
Pang
Zhen
Z
Pang
Zheng
Z
Shilling
Paul D
PD
Melendez
Gilia
G
Schreiber
Rudy
R
Button
Donald
D
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
C490984:Ntsr2 protein, mouse; D018028:Receptors, Neurotensin
J Mol Endocrinol. 2005 Jun;34(3):793-807
15956348
CNS Neurol Disord Drug Targets. 2006 Apr;5(2):205-18
16611093
Neuropsychopharmacology. 2004 Apr;29(4):731-8
14760394
Ann N Y Acad Sci. 1982;400:354-67
6220630
J Pharmacol Exp Ther. 2005 Feb;312(2):733-41
15494551
Psychopharmacology (Berl). 2004 Sep;175(3):353-9
15107967
Brain Res Dev Brain Res. 1999 Mar 12;113(1-2):115-31
10064881
Behav Neurosci. 2006 Oct;120(5):1093-102
17014260
Brain Res. 2010 Jan 13;1308:35-46
19874804
Biol Psychiatry. 2001 Dec 1;50(11):856-72
11743941
J Pharmacol Exp Ther. 1999 Feb;288(2):710-3
9918579
Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
11549226
Schizophr Bull. 1998;24(2):285-301
9613626
Neuropharmacology. 2010 Jan;58(1):173-8
19596359
J Pharmacol Exp Ther. 2005 Oct;315(1):256-64
15987829
Peptides. 2006 Oct;27(10):2476-87
16919370
J Comp Neurol. 2003 Jul 7;461(4):520-38
12746866
Expert Opin Investig Drugs. 2005 Apr;14(4):359-69
15882113
J Neurosci. 2001 Jan 15;21(2):601-8
11160439
J Neurochem. 2007 Sep;102(5):1669-1676
17697051
Neuropharmacology. 2010 Jun;58(8):1199-205
20211191
J Neurosci. 1998 Oct 15;18(20):8394-401
9763482
Behav Brain Res. 2003 Jul 14;143(1):7-14
12842291
Psychopharmacology (Berl). 1988;94(4):507-14
3131796
Neuropharmacology. 2010 Jun;58(7):1174-8
20193696
J Psychiatry Neurosci. 2006 Jul;31(4):229-45
16862241
CNS Drugs. 2007;21(1):13-23
17190526
Arch Gen Psychiatry. 1990 Feb;47(2):181-8
2405807
Behav Brain Res. 2007 Aug 6;181(2):278-86
17559953
Brain Res. 2004 Feb 13;998(1):122-9
14725975
Peptides. 2006 Oct;27(10):2469-75
16872720