Individual differences in running wheel performance and preference for active versus passive reinforcers: role of DARPP32

Abstract

Background: Motivation is characterized by high levels of behavioral activation, vigor, persistence and goal directed behavior. These functions are impair ed in pathologies such as depression or Parkinson disease. Dopamine (DA) in striatum, mainly in nucleus accumbens (Nacb), plays an important role in the regulation o f speed or perseverance in goal - motivated behavior. Studies in animals show that DA depleti ons produce a shift in relative preference between reinforcers that require different levels of behavioral activation, decreasing time spent on a running wheel (RW), and increasing time spent eating. Therefore, differences in basal DA levels could underlin e individual differences in selection of active versus passive reinforcers . Objectives: These studies were conducted to explore a potential relationship between individual differences in voluntary wheel running, striatal (ventral and dorsal) DA activity, and selection of reinforcers with different levels of behavioral activation and effort r equirement. In addition, anxiety, and exploration activity levels were compared betwe en different groups of runners. Methods: CD1 male mice were used in these experiments. All animals were assessed in a Dark and Light box to evaluate anxiety - like behavior , in an Open Field (OF) to assess exploration . After these tests, and during 4 weeks of testing (2 hours a day/5days a week), animals were allowed to run on a running wheel ( RW ) . Different activity groups were determined using first and fou rth quartiles of the average running counts. T he n the th ree choice T - maze task to evaluate spontaneous preferences was used . After these tests, brains were collected and expression of DARPP - 32 phosphorylated at the threonine (Thr) 34 and at Thr 75 residues was assessed immunohistochemically t o provide a marker of DA receptor related metabotropic activity . Results: In the three - choice T - maze task , the high runners spent signif icantly more time in the RW. They had a non - significant tendency to spent less ti me in contact wi th the food . No significant differences were observed in sniffing time. There were no significant differences in anxiety, or OF exploration. Finally, pDARPP32 - Thr34 was lower among the high runners in t he 4 areas of striatum studied. Conclusions: These res ults suggest that differences in basal levels of voluntary exercise are related to preferences for reinforcers that require high levels of activation and effort, and those could be mediated by an increase in DA D2 receptor stimulation . The present results have implications for understanding and treating symptoms such as fatigue, anergia and psychomotor slowing seen in pathologies with a clear motivational component.