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 receptor (mu OR), such as morphine or the endogenous peptide methionine5-enkephalin, can markedly decrease the spontaneous activity of noradrenergic neurons in the locus coeruleus (LC). Messenger RNA and protein for mu OR are also densely expressed by LC neurons. During opiate withdrawal, increased discharge rates of LC neurons coincide with the expression of behavioral features associated with the opiate withdrawal syndrome. To better define the cellular sites for the physiological activation of mu OR in the LC and its relation to afferent terminals, we examined the ultrastructural localization of mu OR immunoreactivity in sections dually labeled for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Immunogold-silver labeling for mu OR (i-mu OR) was localized to parasynaptic and extrasynaptic portions of the plasma membranes of perikarya and dendrites, many of which also contained immunolabeling for TH. The dendrites containing exclusively i-mu OR were more numerous in the rostral pole of the LC. The i-mu OR in dendrites with and without detectable TH immunoreactivity were usually postsynaptic to unlabeled axon terminals containing heterogeneous types of synaptic vesicles and forming asymmetric synaptic specializations characteristic 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-containing neurons in the LC.