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

Agonists of the neuropeptide neurotensin have been proposed as potential no vel antipsychotic; based on their ability to modulate neurotransmission in brain regions associated with schizophrenia. To test this hypothesis, we ex amined the effects of a neurotensin mimetic with improved metabolic stabili ty in an animal model with strong predictive validity far antipsychotic act ivity. Subcutaneous injections of PD149163, a reduced amide neurotensin(8-1 3) mimetic, significantly antagonized the reduction of prepulse inhibition (PPI) of the rat startle reflex produced by amphetamine and by the phencycl idine analog dizocilpine. PD149163 had no significant effect on baseline PP I or on baseline startle amplitude and did not antagonize the reduction of PPI produced by the direct dopamine agonist apomorphine. These findings sug gest that PD149163 has novel antipsychotic-like properties that are distinc t from known members of both the "typical" and "atypical" families of antip sychotics.