The nucleus accumbens (NA), a ventral extension of the striatum, plays a role in several complex behaviour patterns and also is a major site of action of drugs of abuse such as cocaine. Intrinsic NA cells are predominantly quiescent and their activity depends on excitatory input from cortical and subcortical limbic afferents. Here we examine the mechanisms of synaptic plasticity at the synapse between prelimbic cortical afferents and cells in the core region of the NA. Manipulations that induce a Ca(2+)-dependent long-term potentiation (LTP) of non-NMDA (N-methyl-D-aspartate)-receptor-mediated responses also produce a simultaneous long-term depression (LTD) of NMDA-receptor-mediated responses. These results indicate that in a single cell the same change in postsynaptic Ca2+ concentration can have opposite effects on non-NMDA- and NMDA-receptor-mediated synaptic responses. This may be particularly important in the NA, where NMDA receptors are critical for mediating the behavioural actions of drugs of abuse.