Effects of genetic background and environmental novelty on wheel running as a rewarding behaviour in mice

Abstract

Recent studies suggest running wheel activity to be naturally rewarding and reinforcing; considering the shared neuro-behavioural characteristics with drug-induced reward situations, wheel running behaviour gains interest as a tool to study mechanisms underlying reward-sensitivity. Previously, we showed that wheel running has the potential to disrupt the daily organization of home cage behaviour in female C57BL/6 [de Visser L, van den Bos R, Spruijt BM. Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion. Behav Brain Res 2005;160:382-8]. In the present study, we investigated the effects of novelty-induced stress on wheel running and its impact on home cage behaviour in male C57BL/6 and DBA/2 mice. Our aim was to determine whether wheel running may be used as a tool to study both genetic and environmentally induced differences in sensitivity to rewarding behaviour in mice. One group of male mice was placed in an automated home cage observation system for 2 weeks with a wheel integrated in the cage. A second group of mice was allowed to habituate to this cage for 1 week before a running wheel was introduced. Results showed a pronounced sensitising effect of novelty on the level of wheel running in C57Bl/6 mice but not in DBA mice. Overall levels of wheel running were higher in DBA/2 mice. Furthermore, wheel running affected circadian rhythmicity in DBA/2 mice but not in C57BL/6 mice.From these findings we tentatively suggest that wheel running behaviour could serve as a tool to study the interaction between genetic and environmental factors in sensitivity to rewarding behaviour in mice. As it is displayed spontaneously and easy to monitor, wheel running may be well suitable to be included in high-throughput phenotyping assays.

Voluntary Exercise and Sucrose Consumption Enhance Cannabinoid CB1 Receptor Sensitivity in the Striatum

“…Evidence of the rewarding and potentially addictive properties of running wheel is currently accumulating. Rodents, in fact, are highly motivated to gain access to running wheels and display CPP to an environment associated with wheel running (Iversen, 1993;Belke, 1997;Lett et al, 2000;de Visser et al, 2007). Furthermore, animals that run long distances daily show withdrawal signs when access to the running wheels is denied (Hoffmann et al, 1987), and display increased vulnerability for cocaine self-administration and reinstatement after abstinence (Larson and Carroll, 2005).…”

“…Rodents, for example, show CPP to an environment associated with wheel running (Iversen, 1993;Belke, 1997;Lett et al, 2000;de Visser et al, 2007), and show withdrawal signs when access to the running wheels is denied (Hoffmann et al, 1987). The rewarding properties of sucrose drinking are less extensively investigated (Lenoir et al, 2007).…”

“…This finding raises the possibility that other forms of reward-based behaviors may rely on the sensitization of cannabinoid CB1 receptor-mediated transmission in this brain area. Running wheel activity has strong rewarding and reinforcing properties in rodents, and shares many neurochemical and behavioral characteristics with druginduced reward situations, through the modulation of striatal neuron activity (Werme et al, 2000(Werme et al, , 2002Lett et al, 2001;de Visser et al, 2007). It is therefore conceivable that this environmental manipulation mimics the effects of cocaine on cannabinoid-mediated control of striatal synaptic transmission and, in support of this hypothesis, it has been reported that voluntary running wheel exercise activates striatal dopamine (DA) signaling (El Rawas et al, 2009), and increases some behavioral and metabolic effects of cannabinoid CB1 receptor blockade (Zhou and Shearman, 2004).…”

Wheel running, voluntary ethanol consumption, and hedonic substitution

“…C57BL/6J female mice were chosen for this experiment because they consistently consume higher amounts of alcohol and display higher levels of wheel running as compared with C57BL/6J males (Belknap et al, 1993;de Visser et al, 2007). Fifteen female mice were group housed three or four to a standard mouse cage (19.05 × 31.75 × 12 cm).…”

“…These results are in agreement with data reported by Jung et al (2006), indicating that wheel running in (distance and duration) is stable for at least 15 weeks in C57BL/6J mice. It has been shown that intermittent wheel availability or periods of alternating access do not induce a rebound effect on running distance in C57BL/J mice (de Visser et al, 2007).…”