IMPACT OF AGE ON EFFORT MOTIVATED BEHAVIOR AND ON THE CEREBRAL DOPAMINE NEUROTROPHIC FACTOR (CDNF) IN THE NUCLEUS ACCUMBENS

The Cerebral Dopamine Neurotrophic Factor (CDNF) has been demonstrated to have neuroprotective, homeostatic and restorative functions in the nigrostriatal pathway. However, its function in the mesocorticolimbic system, particularly in the Nucleus Accumbens (NAcb), and its potential role in the regulation of motivated behaviors remains poorly understood. We investigated CDNF expression in the NAcb of young and aged CD1 mice of both sexes at baseline and following effortful operant performance for sucrose. In sedentary animals, Western-blot and immunohistochemistry revealed relatively higher CDNF expression in females than males, while aged animals exhibited lower immunoreactivity than young ones. To assess motivated behavior, separate groups were trained in operant chambers to obtain 10% sucrose under varying effort schedules, including a progressive-choice procedure (working for 10% sucrose vs. free 3% sucrose). Results showed that males maintained low lever-pressing performance regardless of age. Conversely, aged females outperformed younger ones, consuming more 10% sucrose. Overall, females significantly outperformed males in both performance and consumption. After training brains were collected, CDNF was analyzed with immunoreactivity techniques. These results show less differences due to age, however, the sex differences persisted, indicating that extended periods of operant training reduce differences due to age but females continue to show a higher level of CDNF in NAcb. Additional experiments are addressing the relation of CDNF with c-Fos and with metabotropic markers of dopamine receptor activity in NAcb. These findings provide insights into neuropsychiatric and neurodegenerative disorders involving impaired motivation and dopaminergic signaling. Grant support: Ministerio de Ciencia e Innovación. PID2021-125977OB-I00, GV-CIGRIS/2023/064.