Age effect on the willingness to work for sucrose in male rats: Involvement of the cerebral dopamine neurotrophic factor

Effort-related symptoms, such as anergia and fatigue, play a central role in many psychopathologies and neurological diseases. The mesolimbic dopamine (DA) pathway projecting to nucleus accumbens, (NAcb) modulates behavioral activation and effort exertion. Depletion of DA levels in Nacb leads to anergia and influences choices toward less effortful demanding options. DA function seems to be diminished with age. Our laboratory has developed behavioral tasks for rodents, including the PROG/sucrose task, for the study of effort-related choices linked to DA signaling in NAcb. Male Wistar rats of different ages were allowed to work lever pressing under different operant schedules for a preferred sucrose solution (5%), or freely drink from a concurrent less preferred sucrose solution (0.3%). The results show that age emerged as a crucial factor reducing the propensity to work for the preferred reinforcer, particularly in the more demanding schedules in older animals (middle to old age). However, older animals consumed more than younger ones of the highly concentrated sucrose when it was freely available. Moreover, there was also an impact of older age on the initial vigor to run in a running wheel (RW), a highly reinforcing activity for rodents. Immunoreactivity analysis of the Cerebral Dopamine Neurotrophic Factor (CDNF), previously involved in the regeneration of the DA nigrostriatal circuit, showed higher immunoreactivity in the Nucleus NAcb core of younger animals. These findings emphasize age-related reductions in the willingness to exert effort or the vigor shown in highly motivating activities, linking it to reduced dopamine-related neurotrophic factors.