ULTRASTRUCTURAL-CHANGES IN RAT LOCUS-COERULEUS INDUCED BY CHRONIC OPIOIDS

The locus coeruleus (LC) is a major noradrenergic nucleus in the brain . The activity of the LC neurons is chronically regulated by opioids. So far, very little is known about the morphological changes induced b y chronic treatment with opioids. In the present study, the effects of chronic treatment with morphine and dihydroetorphine, a new narcotic analgesic with lower physical dependence potential than morphine, were investigated on the ultrastructure of the rat LC. Rats received salin e or increasing doses of morphine or dihydroetorphine for 5 days by tw ice daily subcutaneous injections. Withdrawal was precipitated in half of the opioid-treated rats by a single intraperitoneal injection of n aloxone 4 h after the last injections of opioids. The ultrastructure o f the LC was examined by electron microscopy. Results showed that chro nic morphine treatment induced a marked injury to the LC neurons. The primary changes in the cell body were the indentation of nuclei, the f ragmentation and degranulation of rough endoplasmic reticulum, as well as the disaggregation of polyribosomes. Myelinoid bodies were seen in the processes. An accumulation of presynaptic vesicles was observed i n some of the terminals which formed synaptic junctions with the LC ne urons as compared to the normal controls. Naloxone-precipitated withdr awal from morphine did not stop the morphine-induced injury on the LC neurons except that less accumulation of presynaptic vesicles occurred . Chronic dihydroetorphine treatment only induced a slight change in t he ultrastructure of the LC neurons. These results indicate that the L C neurons are more vulnerable to chronic treatment with morphine than to that with dihydroetorphine.