Ultrastructural changes in adrenaline- and SGC-cells after morphine coincide with alterations of adrenaline and dopamine levels.

The effects of morphine on chromaffin cell ultrastructure and catecholamine contents were studied using the adrenal glands from male mice (ICR strain). After 2 h adrenaline was increased 25% from 8.1 to 11.6 mumol/g tissue, followed by a 50% decrease to 5.2 mumol/g between 8-24 h and low values persisting at 72 h. Dopamine increased initially, reaching peak values of 0.5 mumol/g between 8-24 h, but had returned towards control values of 0.29 mumol/g by 72 h. Noradrenaline remained unchanged at 2.5 mumol/gram. Naloxone prevented alterations in adrenaline and dopamine levels. Ultrastructural examination revealed several types of catecholamine-storing cells. Of these the adrenaline and small-granule chromaffin (SGC) cells were more affected by morphine than noradrenaline cells. While the initial elevation of adrenaline 2 h after morphine was not accompanied by significant ultrastructural changes, the decrease after 8 and 24 h was paralleled by a significant (p less than 0.001) loss of adrenaline granules. Signs of active membrane turnover included an increase in the number of vacuoles, and the appearance of numerous coated omega profiles and coated (77.7 +/- 0.6 nm) vesicles. Clusters of synaptic-like vesicles (59.8 +/- 8.2 nm), slightly larger than neuronal vesicles (45.4 +/- 6.4), increased in the SGC-cells. After 72 h, the chromaffin granules in adrenaline cells remained low in numbers and were heterogeneous in electron density. Many synaptic-like vesicles were aligned along the SGC-cell membranes where only few chromaffin granules (109.3 +/- 20 nm) remained. Thus, continuous morphine exposure for 8-72 h increases the turnover of storage granules in adrenaline and SGC-cells with less effect on the noradrenaline cells which maintain catecholamine levels as indicated by biochemical analysis.