ULTRASTRUCTURAL EVIDENCE FOR PROMINENT DISTRIBUTION OF THE MU-OPIOID RECEPTOR AT EXTRASYNAPTIC SITES ON NORADRENERGIC DENDRITES IN THE RAT NUCLEUS LOCUS-COERULEUS

Physiological studies have indicated that agonists at the mu-opioid re ceptor (mu OR), such as morphine or the endogenous peptide methionine( 5)-enkephalin, can markedly decrease the spontaneous activity of norad renergic neurons in the locus coeruleus (LC). Messenger RNA and protei n for mu OR are also densely expressed by LC neurons. During opiate wi thdrawal, increased discharge rates of LC neurons coincide with the ex pression of behavioral features associated with the opiate withdrawal syndrome. To better define the cellular sites for the physiological ac tivation of mu OR in the LC and its relation to afferent terminals, we examined the ultrastructural localization of mu OR immunoreactivity i n sections dually labeled for the catecholamine-synthesizing enzyme ty rosine hydroxylase (TH). Immunogold-silver labeling for mu OR (i-mu OR ) was localized to parasynaptic and extrasynaptic portions of the plas ma membranes of perikarya and dendrites, many of which also contained immunolabeling for TH. The dendrites containing exclusively i-mu OR we re more numerous in the rostral pole of the LC. The i-mu OR in dendrit es with and without detectable TH immunoreactivity were usually postsy naptic to unlabeled axon terminals containing heterogeneous types of s ynaptic vesicles and forming asymmetric synaptic specializations chara cteristic of excitatory-type synapses. These results provide the first direct ultrastructural evidence that mu OR is strategically localized to modulate the postsynaptic excitatory responses of catecholamine-co ntaining neurons in the LC.