We examined the effect of augmenting the activation of N-methyl-D-aspartate receptors during tetanic stimulation of the corpus callosum. Excitatory postsynaptic potentials were recorded from striatal neurons in an in vitro brain slice bathed in either normal or Mg(2+)-free artificial cerebrospinal fluid. Post-tetanic potentiation was followed by a long-lasting depression of the excitatory postsynaptic potential in normal artificial cerebral spinal fluid. Mg(2+)-free artificial cerebrospinal fluid increased the duration of the pretetanus excitatory postsynaptic potential and the amplitude and duration of the direct response to the tetanus. Mg(2+)-free artificial cerebrospinal fluid also enabled the expression of a short-term potentiation of the excitatory postsynaptic potential amplitude and duration. N-methyl-D-aspartate receptor antagonists blocked the induction of all tetanus-induced excitatory postsynaptic potential changes specific to the Mg(2+)-free artificial cerebral spinal fluid. These results indicate that maintained activation of N-methyl-D-aspartate receptors by synaptically released glutamate can produce a sustained enhancement of the excitatory postsynaptic potential. This use-dependent increase in synaptic efficacy may contribute to basal ganglia-related motor performance.