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

Abstract

Pharmacological blockade of NMDA receptors is used to model certain aspects of schizophrenia. It had been shown previously that ketamine dose dependently enhances high-frequency oscillations in the rodent nucleus accumbens, a structure implicated in schizophrenia. Here, the authors examined the effect of intra-accumbal and systemic administration of MK801 on delta, gamma and high-frequency oscillatory activity recorded in the nucleus accumbens of freely moving rats. In this study, rats were implanted with electrodes in the nucleus accumbens for chronic local field potential recording. Rats received either bilateral injections of MK801 (1 and 4 μg) or intraperitoneal injections of the drug (0.1 and 0.5 mg/kg). Saline was used as control in each instance. Both local and systemic injections significantly enhanced the power and frequency of high-frequency oscillations and caused an increase in the occurrence, duration and amplitude of high-frequency oscillatory bursts. In contrast, no effect or a decrease in the power of delta and gamma bands was observed following local or systemic administration of MK801, respectively. These findings suggest that the dominant change in oscillatory activity after administration of NMDA receptor antagonists affect high frequencies. Moreover, direct NMDA blockade in the accumbal circuitry is sufficient to generate increases in high-frequency oscillations. The presence of abnormal oscillatory activity in the accumbens may be associated with the psychomimetic effects of NMDA receptor antagonists.