The effects of methadone on cortical and subcortical EEG in the rat.

(1) Administration of methadone in rats elicited high voltage, slow activity in the cerebral cortex and low voltage irregular waves in the hippocampus. Intravenous administration of methadone (0.2-0.5 mg/kg) markedly increased the threshold for cortical desynchronization by stimulation of the MRF. This increase by methadone was dose dependent. (2) Cortical desynchronization following mechanical stimulation of the tail or foot was blocked by methadone at a dose level of 0.5 mg/kg. At this dose level, the cortical desynchronizing threshold for MRF stimulation increased more than 8-fold whereas the threshold for MT and DH stimulations showed only small but measurable increases. A minimum dose of 0.5 mg/kg was needed to raise the threshold of these structures significantly (3) The increased threshold following injection of methadone was completely blocked by prior injection of the antagonist naloxone, indicating this response to be specific. Naloxone alone had no effect on electrical activity at any site. (4) The incidence of dissociation of the cortical response from the limbic system response after stimulation of the dorsal hypothalamus was approximately 4 times greater in methadone-treated than in untreated animals.