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Research ArticleArticle

Novel Antipsychotic-Like Effects on Prepulse Inhibition of Startle Produced by a Neurotensin Agonist

David Feifel, Tammi L. Reza, David J. Wustrow and M. Duff Davis
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 710-713;
David Feifel
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Tammi L. Reza
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David J. Wustrow
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M. Duff Davis
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Abstract

Agonists of the neuropeptide neurotensin have been proposed as potential novel antipsychotics based on their ability to modulate neurotransmission in brain regions associated with schizophrenia. To test this hypothesis, we examined the effects of a neurotensin mimetic with improved metabolic stability in an animal model with strong predictive validity for antipsychotic activity. Subcutaneous injections of PD149163, a reduced amide neurotensin(8–13) mimetic, significantly antagonized the reduction of prepulse inhibition (PPI) of the rat startle reflex produced by amphetamine and by the phencyclidine analog dizocilpine. PD149163 had no significant effect on baseline PPI or on baseline startle amplitude and did not antagonize the reduction of PPI produced by the direct dopamine agonist apomorphine. These findings suggest that PD149163 has novel antipsychotic-like properties that are distinct from known members of both the “typical” and “atypical” families of antipsychotics.

Footnotes

  • Send reprint requests to: David Feifel, M.D., Ph.D., Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-8620. E-mail:dfeifel{at}ucsd.edu

  • ↵1 This work was supported by a National Alliance for Research in Schizophrenia and Depression grant (D.F.).

  • Abbreviations:
    PPI
    prepulse inhibition
    ANOVA
    analysis of variance
    PCP
    phencyclidine
    NMDA
    N-methyl-d-aspartate
    • Received April 8, 1998.
    • Accepted July 20, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Novel Antipsychotic-Like Effects on Prepulse Inhibition of Startle Produced by a Neurotensin Agonist

David Feifel, Tammi L. Reza, David J. Wustrow and M. Duff Davis
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 710-713;

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Research ArticleArticle

Novel Antipsychotic-Like Effects on Prepulse Inhibition of Startle Produced by a Neurotensin Agonist

David Feifel, Tammi L. Reza, David J. Wustrow and M. Duff Davis
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 710-713;
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