Novel antipsychotic-like effects on prepulse inhibition of startle produced by a neurotensin agonist

David Feifel, Tammi L. Reza, David J. Wustrow, 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.

Original languageEnglish (US)
Pages (from-to)710-713
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number2
StatePublished - Feb 1 1999

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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