BACKGROUND AND AIMS: Non-competitive NMDA receptor (NMDAR) antagonists such as dizocilpine (MK801) are widely used to model schizophrenia in animals. The disease is thought to be associated with abnormal activity of several brain areas including the medial prefrontal cortex (mPFC), hippocampus, amygdala and nucleus accumbens (NAc). Of these, the mPFC is one of the most important structures, as its efferent pathways are considered to exert a top-down regulatory control of other limbic structures. NMDAR antagonists induce abnormal neuronal activity, e.g. they enhance high frequency oscillations (HFO, 130–180 Hz) in the NAc. It is unclear whether HFO are independently generated in NAc or are modulated by an afferent excitatory transmission from e.g. the mPFC. To address this issue, we used local infusion of tetrodotoxin (TTX) or picrotoxin (PIC) to mPFC to determine whether changes in the prefrontal neurons activity influence the power and frequency of HFO recorded in the NAc. METHODS: Male Wistar rats were bilaterally implanted with guide cannulas and electrodes in the mPFC and electrodes in the right NAc. MK801, PIC and TTX (preceded by ip injection of MK801) were infused into mPFC. In freely moving rats local field potentials were recorded in NAc and mPFC. The effect of infusions on power and frequency of HFO in the NAc was evaluated. RESULTS: Bilateral (mPFC) administration of MK-801 produced a substantial increase in the power of HFO in the NAc. No change, in relation to control group, in the power of HFO was observed in the NAc after infusion of TTX or picrotoxin into the mPFC. CONCLUSIONS: Generation of HFO in NAc does not depend on the activity in the mPFC. However, MK801-induced disturbance in the neuronal activity in the mPFC may cause changes in accumbal HFO, suggesting that generation of HFO may be modulated by afferent signal from mPFC.
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