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
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|