CROSS-CELLULAR ADAPTATION TO METHADONE AND MEPERIDINE IN CEREBRAL CORTICAL SLICES FROM MORPHINIZED RATS

¹ Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York

Meperidine did not alter the respiratory rate of unstimulated cortical slices at concentrations between 5 x 10^-4 and 1 x 10^-3 M, but these concentrations had a depressive effect on the respiratory rate of KCl-stimulated cortical slices.

Methadone had a diphasic action on the respiratory rate of unstimulated cortical slices, stimulating at 2 x 10^-4 and 5 x 10^-4 M and depressing at concentrations above 1 x 10^-3 M. Methadone depressed the KCl-stimulated respiratory rate of cortical slices at a concentration (1 x 10^-4 M) which did not affect the unstimulated rate.

Complete cross-cellular adaptation was seen with methadone in cortical slices adapted to the depressive effect of morphine. There was only a partial cross-adaptation to meperidine. The adaptation to morphine, methadone and meperidine was acutely reversed by an injection of nalorphine to the morphinized rats prior to sacrifice.