Ketamine dose-dependently induces high-frequency oscillations in the nucleus accumbens in freely moving rats

In humans, subanesthetic doses of ketamine and recovery from ketamine anesthesia are associated with psychotic-like behavior. In rodents, ketamine produces hyperactivity, stereotypies, and abnormal social interaction used to model certain features of schizophrenia. Increasing evidence has implicated aberrant activity in the nucleus accumbens (NAc) with the pathophysiology of schizophrenia.

Here, we examined the effect of an IP injection of ketamine (10, 25, 50, and 200 mg/kg) and d-amphetamine (3 mg/kg) on local field potentials in the rodent NAc. Locomotor activity was recorded simultaneously.

Spontaneous high-frequency oscillations (HFO) (140-180 Hz) were present in local field potentials recorded from the NAc. Ketamine dose-dependently induced rapid and substantial increases in HFO that correlated with behavioral hyperactivity. Similarly, large increases in HFO occurred during recovery from ketamine anesthesia. In contrast, d-amphetamine, which induced locomotor activity, produced only small increases in HFO.

We propose that ketamine-induced abnormal increases in HFO form part of the complex neurological changes in this model of schizophrenia. Ketamine-induced increases in HFO, although sharing similar temporal dynamics to hyperactivity, may not be functionally related to increased movement.