We have previously shown that ketamine, a drug that produces psychotic activity in humans, can enhance high-frequency oscillations (HFO) in the rat nucleus accumbens (NAc). To date, the effect of ketamine on HFO recorded in other structures is unknown. In the present study, we have used a variety of techniques, including monopolar and bipolar local field potential recordings, inverse current source density and a modeling study to examine the changes in oscillatory activity that occur in the hippocampus (and surrounding tissue) and dorsal and ventral striatum. Our data provide the first evidence that ketamine produces regionally selective increases in HFO that occurs in the NAc. Although ketamine-associated HFO can be recorded in distant structures they do not appear to be generated at these recording sites. In contrast, the occurrence of spontaneous hippocampul HFO (known as ripples) was reduced by ketamine, but this change is likely to be secondary to the hyperlocomotion induced by ketamine injection. The functional correlate of HFO is unclear, but it is plausible that this oscillation by modifying online information processing in the NAc, may be associated with the psychotomimetic activity of the drug.