Reward related dysfunctions and cognitive alterations represent the first cause of therapy discontinuation in patients with major depression disorders and schizophrenia, and pharmacological interventions employed to treat these symptoms are often limited by the poor tolerability in the long-term period. In the last years, several clinical evidence have highlighted a link between a reduced level of n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and the aforementioned psychiatric conditions. However, the implication of these lipids in the etiology of cognitive and reward-related dysfunctions has still to be clarified. A major neurobiological mechanism that is considered to be critical in the origin of these symptoms is an impaired dopaminergic neurotransmission at both cortical and striatal levels. In order to assess whether the n-3 PUFA deficiency entailed some perturbations of dopaminergic activity in these regions, we performed multi-site microdialysis to measure basal and stimulated release of dopamine in the Nucleus Accumbens (NAc) and Prefrontal Cortex (PFC) of n-3 PUFA deficient mice. We found that, while the n-3 PUFA deficiency does not impair dopaminergic neurotransmission in the NAc, it profoundly affects that of the PFC, with blunted amphetamine-stimulated release of dopamine and altered turnover. Furthermore, since cortical dopaminergic hypofunction is considered to play a major role in the expression of cognitive dysfunctions in many psychiatric conditions, we evaluated whether n-3 PUFA deficient mice displayed comparable behavioral alterations. Using a specific satiety outcome-devaluation paradigm we showed that n-3 PUFA deficient mice are compromised in their ability to perform goal-directed actions.