Effects of scopolamine in comparison with apomorphine and phencyclidine onprepulse inhibition in rats

The potential involvement of the muscarinic cholinergic system in the under lying mechanisms of prepulse inhibition of the acoustic startle reflex was evaluated in male Sprague-Dawley rats under conditions of varying dose, pre pulse intensity, and interstimulus interval. The effects of scopolamine on prepulse inhibition were also directly compared with the effects observed u sing apomorphine and phencyclidine under the same test parameters. Scopolam ine (0.03-1.0 mg/kg) produced a significant dose-dependent decrease in prep ulse inhibition, but had no effect on startle amplitude over the dose range tested. Apomorphine (0.03-1.0 mg/kg) and phencyclidine (0.1-5.6 mg/kg) pro duced significant dose-dependent decreases in prepulse inhibition and chang es in startle amplitude. The scopolamine-induced decrease in prepulse inhib ition varied with prepulse intensity in that the changes produced by scopol amine became smaller in magnitude as the prepulse intensity was increased f rom 9 to 30 dB above background. On the other hand, apomorphine and phencyc lidine decreased prepulse inhibition to approximately the same magnitude ac ross all prepulse intensities tested. The observed decreases in prepulse in hibition produced by scopolamine, apomorphine, acid phencyclidine were also dependent on interstimulus interval duration. Scopolamine produced marked decreases in prepulse inhibition at the 100- and 300-ms interstimulus inter val durations, but had Little or no effect on prepulse inhibition at the 30 - and 1000-ms interstimulus interval durations. In contrast, apomorphine de creased prepulse inhibition across all interstimulus interval durations whi le phencyclidine decreased prepulse inhibition across the 30- to 300-ms int erstimulus interval durations. The present findings support the hypothesis that the muscarinic cholinergic system, like the dopaminergic and glutamate rgic systems, is directly involved in the mechanisms of prepulse inhibition . However, these three neurotransmitter systems appear to modulate differen t aspects of prepulse inhibition. (C) 2000 published by Elsevier Science B. V. All rights reserved.