Volume 16, Number 16,
Issue of August 15, 1996
pp. 5037-5048
Copyright ©1996 Society for Neuroscience
Ultrastructural Evidence for Prominent Distribution of the
µ-Opioid Receptor at Extrasynaptic Sites on Noradrenergic Dendrites
in the Rat Nucleus Locus Coeruleus
Received Feb. 6, 1996; revised May 9, 1996; accepted May 21, 1996.
Elisabeth J. Van Bockstaele1,
Eric E. O. Colago1,
Peter Cheng1,
Akiyoshi Moriwaki2,
George R. Uhl2, and
Virginia M. Pickel1
1 Department of Neurology and Neuroscience, Cornell
University Medical College, New York, New York 10021, and
2 National Institute on Drug Abuse, Division of Intramural
Research Program, Addiction Research Center, Baltimore, Maryland
21224
Physiological studies have indicated that agonists at the
µ-opioid receptor (µOR), 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 µOR 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 µOR in the LC and its
relation to afferent terminals, we examined the ultrastructural
localization of µOR immunoreactivity in sections dually labeled for
the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH).
Immunogold-silver labeling for µOR (i-µOR) 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-µOR were more numerous
in the rostral pole of the LC. The i-µOR 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 µOR is strategically localized to
modulate the postsynaptic excitatory responses of
catecholamine-containing neurons in the LC.
Key words:
norepinephrine;
drug abuse;
enkephalin;
opiate;
morphine;
excitatory amino acid