Interactive effects of MK-801 and morphine on EEG, EEG power spectra and behavior in rats: I. Morphine tolerance development

This study investigated a potential interaction between MK-801 and morphine tolerance using electroencephalography (EEG), EEG spectral parameters and behavior in the rat. Rats were treated for 7 days with morphine alone or with morphine and MK-801. Control groups receive chronic MK-801 alone or saline. On day 8 all rats received morphine alone. Co-treatment significantly accelerated the development of tolerance to morphine-induced total power and latency to sleep onset. Co-treatment, but not morphine alone, produced tolerance to morphine-induced complexity and edge frequency, and produced tolerance equal to that from morphine alone in duration of EEG bursting. MK-801 co-treatment decreased, where chronic morphine alone increased, the excitatory response to morphine. Our results support recent reports that chronic morphine treatment produces supersensitivity to glutamate in the rat cortex and alteration in mesolimbic dopamine levels that are modulated by glutamatergic activity.