Effects of morphine and methadone treatments on glutamatergic transmission in rat frontal cortex

The effects of repeated administration of morphine and methadone, followed by a challenge dose of either morphine or methadone were examined ex vivo in rat frontal cortical slices that were prepared 1 h after final drug administration. Morphine challenge dose (5 mg/kg), administered 14 days after the end of repeated morphine pretreatment (10 mg/kg, administered 7 times) decreased both the AMPA/kainate and the NMDA components of field potentials that were evoked in cortical layer II/III by electrical stimulation. This effect did not occur either when a methadone challenge dose (2.5 mg/kg) was administered instead of morphine or after repeated morphine treatment. Moreover, after repeated methadone treatment (2.5 mg/kg, administered 7 times), neither morphine nor methadone challenge affected AMPA/kainate or NMDA components of the field potentials. These data indicate a specific effect of repeated morphine followed by morphine challenge on cortical glutamatergic transmission.