Comparison of apomorphine, amphetamine and dizocilpine disruptions of prepulse inhibition in inbred and outbred mice strains

The dopamine agonist apomorphine robustly disrupts prepulse inhibition of t he acoustic startle response in the rat, yet published studies have not dem onstrated a robust disruption of prepulse inhibition with apomorphine in th e mouse. The aim of these studies was to establish the optimal prepulse con ditions (using manipulations to prepulse intensity and inter-stimulus inter val) and mouse strain(s) for testing apomorphine, and also the prepulse inh ibition disrupting drugs amphetamine, and dizocilpine (NIK-801). The effect s of these drugs on startle response and prepulse inhibition were tested in outbred CD-1 and Swiss Webster (CFW) strains, and the inbred C57BL/6, 129X 1/SvJ, and A/J strains. There were strain differences with baseline startle and prepulse inhibition in that the CD-1, CFW, and C57BL/6 strains exhibit ed high levels of startle and prepulse inhibition, the 129X1/SvJ strain exh ibited low levels of startle but high levels of prepulse inhibition, while the A/J strain exhibited low startle and no prepulse inhibition. Apomorphin e disrupted prepulse inhibition in the CFW and C57BL/6 strains and the effe ct was only evident when using a short 30 ms inter-stimulus interval. Amphe tamine disrupted prepulse inhibition in the CFW. C57BL/6, and 129X1/SvJ str ains, and dizocilpine disrupted prepulse inhibition in the CD-1, CFW, C57BL /6, and 129X1/SvJ strains. The effects of amphetamine and dizocilpine were independent of the inter-stimulus interval. These studies demonstrated clea r strain differences in the startle response and prepulse inhibition, and t he pharmacological disruptions of prepulse inhibition, and suggest that int er-stimulus intervals less than 100 ms may be optimal for detecting the eff ects of apomorphine in mice. (C) 2001 Published by Elsevier Science B.V.