Strain-specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice

Several reports describe substantive behavioral differences between strains of mice both at baseline and in response to pharmacological manipulations. For example, mouse strain differences have been reported in prepulse inhibition (PPI) and patterns of locomotor activity, two behavioral processes that are altered by dopamine (DA) agonists such as amphetamine. Here, we characterized acoustic and tactile startle reactivity, acoustic PPI, and both the amounts and spatial patterns of locomotor activity in C57BL/6J, 129SvEv (129S6), and 129SvJ (129X1) mice at baseline and in amphetamine dose-response studies. Because hearing loss is common in numerous strains of mice, we also assessed cross-modal PPI using a light prepulse with an airpuff startle stimulus. The results establish that these three inbred strains of mice display both intra- and cross-modal PPI, and that amphetamine decreases PPI and startle reactivity in a dose-, sensory modality-, and strain-specific manner. Furthermore, the amount of locomotor activity and the spatial pattern of motor sequences are altered differentially after treatment with amphetamine in C57BL/6J and 129X1 mice, but not in 129S6 mice. Given that amphetamine releases presynaptic DA, these findings are consistent with the role of DA in the modulation of PPI and motor patterns in mice. These findings highlight the importance of selecting appropriate strains of mice for behavioral, pharmacological, and genetic studies.