Neuronal sensitivity to opiate and opioid peptides in the bed nucleus of the stria terminalis. Effects of chronic treatment with morphine.

To characterize the phenomenon of morphine tolerance in central nervous system, the neuronal sensitivity to opiate and opioid peptides in the bed nucleus of the stria terminalis (BST) and the effects of chronic treatment with morphine were examined with thin slices of the brain of guinea pigs. Both morphine and enkephalins (D-Ala2-Met5-enkephalinamide and D-Ala2-D-Leu5-enkephalin) suppressed neuronal activity in the stria terminalis. Three days after implantation of morphine pellets the guinea pigs became tolerant to morphine and EC50 (the morphine concentration required for causing 50% of the maximal effect) was 79 microM, nearly six times the value in the control animals (EC50 = 13 microM). Cross-tolerance between morphine and enkephalins was not observed. Results of radioreceptor assay, using [3H]dihydromorphine as a ligand, showed that the binding capacity of the morphine-tolerant animals was not statistically different from that of the controls. These results suggested that tolerance to morphine cannot be explained by changes in number and/or affinity of opiate receptors, and that tolerance probably results from modification of the intracellular mechanisms mediating between the binding of morphine with the receptors and neuronal inhibition.