PMID- 19596359
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20211020
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 58
IP  - 1
DP  - 2010 Jan
TI  - Sensorimotor gating in neurotensin-1 receptor null mice.
PG  - 173-8
LID - 10.1016/j.neuropharm.2009.07.002 [doi]
AB  - BACKGROUND: Converging evidence has implicated endogenous neurotensin (NT) in the 
      pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition 
      of the startle reflex (PPI) is a measure of sensorimotor gating and considered to 
      be of strong relevance to neuropsychiatric disorders associated with psychosis 
      and cognitive dysfunction. Mice genetically engineered to not express NT display 
      deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 
      receptors have been most strongly implicated in mediating the psychosis relevant 
      effects of NT such as attenuating PPI deficits. To investigate the role of NT1 
      receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and 
      NT1 knockout (KO) mice. We also tested the effects of amphetamine and 
      dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce 
      PPI as well as the NT1 selective receptor agonist PD149163, known to increase PPI 
      in rats. METHODS: Baseline PPI and acoustic startle response were measured in WT 
      and NT1 KO mice. After baseline testing, mice were tested again after receiving 
      intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 
      10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 
      mg/kg) on separate test days. RESULTS: Baseline PPI and acoustic startle response 
      in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice 
      exhibited similar responses to the PPI-disrupting effects of dizocilpine and 
      amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the 
      acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS: The 
      data does not support the regulation of baseline PPI or the PPI disruptive 
      effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 
      receptor, although they support the antipsychotic potential of pharmacological 
      activation of NT1 receptors by NT1 agonists.
FAU - Feifel, D
AU  - Feifel D
AD  - Department of Psychiatry, University of California, San Diego, Medical Center, 
      200 West Arbor Drive, San Diego, CA 92103-8218, USA. dfeifel@ucsd.edu
FAU - Pang, Z
AU  - Pang Z
FAU - Shilling, P D
AU  - Shilling PD
FAU - Melendez, G
AU  - Melendez G
FAU - Schreiber, R
AU  - Schreiber R
FAU - Button, D
AU  - Button D
LA  - eng
GR  - R01 MH080910/MH/NIMH NIH HHS/United States
GR  - R01 MH080910-01A2/MH/NIMH NIH HHS/United States
GR  - MH080910/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090709
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Indoles)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (PD 149164)
RN  - 0 (Receptors, Neurotensin)
RN  - 0 (neurotensin type 1 receptor)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - CK833KGX7E (Amphetamine)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Acoustic Stimulation/adverse effects
MH  - Adamantane/analogs & derivatives/pharmacology
MH  - Amphetamine/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Central Nervous System Stimulants/pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Indoles/pharmacology
MH  - Mice
MH  - Mice, Knockout/physiology
MH  - Neural Inhibition/drug effects/*genetics
MH  - Neuroprotective Agents/pharmacology
MH  - Receptors, Neurotensin/*deficiency
MH  - Reflex, Startle/drug effects/*genetics
MH  - Sensory Gating/drug effects/*genetics
PMC - PMC2784210
MID - NIHMS131268
EDAT- 2009/07/15 09:00
MHDA- 2010/02/26 06:00
PMCR- 2011/01/01
CRDT- 2009/07/15 09:00
PHST- 2009/05/19 00:00 [received]
PHST- 2009/06/29 00:00 [revised]
PHST- 2009/07/02 00:00 [accepted]
PHST- 2009/07/15 09:00 [entrez]
PHST- 2009/07/15 09:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0028-3908(09)00209-3 [pii]
AID - 10.1016/j.neuropharm.2009.07.002 [doi]
PST - ppublish
SO  - Neuropharmacology. 2010 Jan;58(1):173-8. doi: 10.1016/j.neuropharm.2009.07.002. 
      Epub 2009 Jul 9.