Nucleus Accumbens (Nacb) dopamine (DA) regulates behavioral activation and effort-related decision-making in motivated behaviors. DA depletion has been shown to induce anergia and fatigue in effort-based decision tasks. The Cerebral Dopamine Neurotrophic Factor (CDNF) promotes the survival and function of dopaminergic neurons, and it is used to restore midbrain dopaminergic neurons in animal models of Parkinson’s disease. However, little is known about the role of CDNF in Nacb and if this neurotrophic factor can be affected by factors such as sex or age, behavioral manipulations or drugs that modulate DA transmission. Our results show that baseline CDNF immunoreactivity does not differ between sexes in both types of rodents, but it is reduced with age. In addition, CDNF was reduced after the administration of the DA depleting agent Tetrabenazine (TBZ) or DA receptor antagonists. However, long term operant training and environmental enrichment increased CDNF in Nacb. We also characterized the neuroanatomical distribution of CDNF in Nacb under baseline conditions. Our results show that, in Nacb, CDNF seems to concentrate mainly in postsynaptic but not in presynaptic neurons. Its immunoreactivity is collocalized with DAPI and NeuN, and with enkephalin, substance P and parvalbumin gabaergic neurons, but not with TH and DAT positive neurons. These preliminary results indicate that CDNF could be involved in DA related postsynaptic Nacb neurons, since conditions that increase DA function such as operant training or voluntary running increase CDNF immunoreactivity and conditions that reduce DA function such as age and DA depletion or antagonists reduce CDNF.