Local injection of MK801 modifies oscillatory activity in the nucleus accumbens in awake rats

Oscillatory activity of the electrical potentials recorded in the brain is believed to be essential for the proper processing of information. In recent years, high frequency oscillations (HFO >130 Hz) have been reported in a variety of brain regions and these oscillations are emerging as an important field of research to understand normal and pathological brain states. We have shown previously that HFO also occur in the nucleus accumbens (a brain region implicated, among others in schizophrenia and drug abuse) and can be markedly enhanced by systemic injection of NMDA receptor antagonists. This latter finding is of particular interest since subanesthetic doses of NMDA receptor antagonists, such as ketamine, are used widely to model certain aspects of schizophrenia in both humans and experimental animals. Therefore, understanding the nature of the abnormal oscillatory activity in this experimental model may shed light on the underlying neural network disturbances associated with schizophrenia.

In the present study, we show that local injection of the NMDA receptor antagonist, MK801, to the accumbens is sufficient to enhance the power and frequency of HFO, comparable to values after systemic injection. The substantial increase in the amplitude of HFO (typically 10-fold compared to baseline) probably reflects the generation of HFO by more numerous or larger clusters of neurons in the accumbens. Interestingly, we observed no increase in the power of delta and gamma frequency bands, after local injection, indicating NMDA receptor antagonists preferentially enhance HFO in the accumbens. These findings show that NMDA antagonists can act directly to modify the intrinsic circuitry of the accumbens leading to the generation of HFO. Further studies are warranted to determine precisely how this class of compounds influences the activity of individual accumbal neurons.

29 December 2010