Methadone-induced changes in the visual evoked response recorded from multiple sites in the cat brain

Visual evoked responses (VERs) and EEG were recorded following the i.p. administration of five doses of methadone (0.5--4 mg/kg) to 12 adult cats, which were implanted with cortical and subcortical electrodes. Additional cats, subjected to the same drug regimen, were used to evaluate plasma methadone concentrations. Doses of methadone that produced plasma concentrations between 80 and 190 ng/ml differentially affected VERs recorded from cortical and subcortical sites. Of the subcortical structures evaluated, the limbic system, specifically the hippocampus, was the most sensitive to the effects of the drug. These effects appeared to be primarily depressant. Responses recorded from the reticular formation and centromedian were affected only by the highest dose of methadone, while VERs recorded from cortical sites were reliably altered following the two highest doses and appeared to reflect both excitation and depression. Behavioral changes, however, were clearly evidenced in some cats at lower doses of methadone. Therefore, the data suggest (1) that those structures evaluated electrophysiologically did not reflect the full force of the drug's action as evidenced by its effect on behavior, (2) that cortical and subcortical recording sites have differential sensitivities, and (3) that one clearly defined, principal size of action of methadone is absent in the cat.