Acoustic startle and disruption of prepulse inhibition by dizocilpine in selectively bred mice

In this study we examined the relationship between genetically produced differences in the magnitude of prepulse inhibition (PPI) of the acoustic startle response (ASR) and stress induced swim analgesia in genetically different strains of mice. Prepulse inhibition of the ASR and its changes due to dizocilpine (MK-801) injection were studied in 180 mice. The animals used in this study were obtained from our colony of 54 generation, Swiss-Webster mice selectively bred for high and low magnitude of analgesia. Three month old male mice of the high analgesia (HA) and the low analgesia (LA) lines, in addition to randomly bred controls (C), were used in the experiment. Thirty minutes before the ASR session the mice were injected intraperitoneally with saline or with 0.15, 0.25, 0.5 mg/kg of dizocilpine maleate. Prepulses suppressed the acoustic startle response in all lines in a prepulse intensity-dependent manner, but only the differences between the weakest and the strongest prepulses appeared significant. Two-way ANCOVA performed separately for each line revealed a significant effect of dizocilpine and prepulse intensity. Only in the HA line, however, the disruption of PPI from the injection of dizocilpine was evidenced by significant treatment by prepulse interaction. That means the prepulses decreased ASR significantly less in dizocilpine- treated animals than in saline-treated animals. The results confirmed that the mouse lines manifesting differential ASR magnitudes along with different degrees of PPI sensitivity to dizocilpine, might be suitable for pharmacogenetic studies on the glutaminergic mechanism of the startle response.