Differential effects of voluntary exercise and housing density on anxiety-like behavior in C57Bl/6 mice

The interaction of voluntary exercise and housing density on a) anxiety-like behavior and b) the stimulant effects of methamphetamine in C57Bl/6 mice were evaluated. Upon arrival, mice were housed singly or in pairs, and permitted access to home-cage running wheels or not for 4 weeks. Testing for anxiety-like behavior occurred over the next 3 weeks, one test per week [Elevated-Plus Maze (EPM) → Hyponeophagia (HNP) task → Open-Field (OF) task]. The final, OF task involved an 8-hour session in which mice were permitted to explore the chamber (drug free) during Hours 1-3; given an injection (s.c.) of methamphetamine (1.0 mg/kg) after Hour 3; followed by continued behavioral sampling during Hours 4-8. Several tasks (HNP and OF, but not EPM) consistently showed voluntary exercise induced anxiety-like behavior. In addition, two measures (time in center and time resting in the perimeter) in the OF task revealed that exercise mice compared to controls were more responsive to the anxiogenic effects of methamphetamine. Although pair housing was anxiolytic, it did not ameliorate the anxiogenic effects of voluntary exercise. Taken together, these results, when viewed in tandem with previous studies that utilized a less anxious mouse strain (Swiss Webster), may suggest that voluntary exercise is anxiogenic in an anxiety-prone mouse strain such as C57Bl/6 and highlight the importance of considering mouse strain when evaluating the impact of environmental manipulations on anxiety-like behavior in animal models.