Effects of acute and continuous morphine administration on the affinity of glutamic acid decarboxylase for pyridoxal 5′-phosphate

Abstract

The studies showed that neither morphine nor naloxone at concentrations up to 10 −3 M exhibited any effect on the affinity of glutamic acid decarboxylase (GAD) for its cofactor, pyridoxal 5′-phosphate (P-5′-P) in vitro. Acute administration of morphine sulfate with respect to time course and dose-response studies also failed to modify the affinity of GAD for P-5′-P. In contrast, in mice rendered tolerant to morphine by morphine pellet implantation there was a significant attenuation in affinity of GAD for P-5′-P. The sensitivity of this enzyme for P-5′-P during the course of the development of tolerance to morphine was restored partially either when the morphine was abruptly withdrawn by removing the morphine pellet or when withdrawal was precipitated by naloxone. The recovery of the affinity of GAD for its cofactor was shown to be naloxone dose-dependent. These results further substantiate that the γ-aminobutyric acid (GABA) system may be involved in morphine tolerance and the development of dependence.