Neurotensin-Deficient Mice Have Deficits in Prepulse Inhibition: Restoration by Clozapine but Not Haloperidol, Olanzapine, or Quetiapine

@article{Kinkead2005NeurotensinDeficientMH,
  title={Neurotensin-Deficient Mice Have Deficits in Prepulse Inhibition: Restoration by Clozapine but Not Haloperidol, Olanzapine, or Quetiapine},
  author={Becky Kinkead and Paul R. Dobner and Vasili Egnatashvili and T. Scott Murray and N Deitemeyer and Charles B. Nemeroff},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2005},
  volume={315},
  pages={256 - 264}
}
  • B. Kinkead, P. Dobner, C. Nemeroff
  • Published 1 October 2005
  • Psychology, Biology, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
Prepulse inhibition (PPI) of the acoustic startle reflex is a commonly used measure of preattentive sensorimotor gating. Disrupted PPI in rodents represents an animal model of the sensorimotor gating deficits characteristic of schizophrenia. The neurotensin (NT) system is implicated in the pathophysiology of schizophrenia, and NT has been hypothesized to act as an endogenous antipsychotic. In rats, NT receptor agonists restore PPI disrupted by dopamine receptor agonists and N-methyl-d-aspartate… 

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References

SHOWING 1-10 OF 52 REFERENCES
Neurotensin: dual roles in psychostimulant and antipsychotic drug responses.
Neurotensin-deficient mice show altered responses to antipsychotic drugs
TLDR
It is demonstrated that the ability of the typical APD haloperidol to induce Fos expression in the dorsolateral striatum is markedly attenuated in NT-null mutant mice, consistent with the hypothesis that endogenous NT mediates a specific subset of APD actions.
Enhanced Neurotensin Neurotransmission Is Involved in the Clinically Relevant Behavioral Effects of Antipsychotic Drugs: Evidence from Animal Models of Sensorimotor Gating
TLDR
It is demonstrated that NT neurotransmission is critically involved in the behavioral effects of antipsychotic drugs in two models of antippsychotic drug activity: disrupted prepulse inhibition of the acoustic startle response (PPI) and the latent inhibition (LI) paradigm, and suggest that neurotensin receptor agonists may represent a novel class of antip psychosis drugs.
Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia.
TLDR
Several different ways the loss of PPI in rats can be used as a model for studying the pathophysiology and neurobiology of impaired sensorimotor gating in schizophrenia patients and for predicting antipsychotic activity in novel compounds are described.
Mouse genetic models for prepulse inhibition: an early review
TLDR
This review provides a synopsis of the use of mouse models to explore genetic and neurochemical influences on PPI and finds that mutant mice are important tools for dissecting and studying the role of single genes and their products, and chromosomal regions in regulating PPI.
The effects of intra-accumbens neurotensin on sensorimotor gating
The neurotensin antagonist SR 48692 attenuates haloperidol-induced striatal Fos expression in the rat
Novel antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist.
TLDR
It is suggested that PD149163 has novel antipsychotic-like properties that are distinct from known members of both the "typical" and "atypical" families of antipsychotics.
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