Individual differences in running wheel performance are related to preferences for active reinforcers: the role of Nucleus Accumbens CDNF.

Abstract

Exercise has been demonstrated to have a positive impact on psychological well-being and mental health. Nucleus Accumbens (Nacb) dopamine (DA) has been implicated in regulating the energizing component of motivated behavior, including effort-related decision making, both in humans and rodents. It has been shown in rats that selection of effortful operant options correlated with changes in DA related markers in Nacb. In addition, exercise seems to prevent or help to improve motivational symptoms such as fatigue and anergia. In the present study, we evaluated the relationship between individual differences in endurance on a voluntary running wheel (RW), and differences in Nacb parameters related to DA in adult male CD1 mice. Performance was evaluated during 2 hours per day, 5 days a week during 4 weeks. Mice were selected based on the second hour performance as high runners (HR, first quartile) and low runners (LR, forth quartile). Behavioral phenotyping was performed before animals started training. Thus, mice were evaluated in paradigms of anxiety, sociability and novelty induced exploration in an open field. After training, animals were assessed in a T-maze RW task in which rodents can chose between RW vs. sedentary activities such as consuming sucrose or sniffing a neutral odor. HR spent significantly more time in the RW, and less time in contact with the sedentary reinforcers (sucrose and odor) compared to LR. HR also were indifferent to social stimuli compared to LR, but there were no differences in other behaviors. Cerebral dopamine neurotrophic factor (CDNF) in Nacb was higher among HR. These results suggest that differences in basal levels of voluntary exercise increase predisposition to choose more active reinforcers that require high levels of activation and effort, and indicate that differences in neurotrophic factors can sustain differences in DA function.