In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I-II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a functional role in the physiology of this structure.