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Journal of Neuroscience, Vol 7, 2445-2464, Copyright © 1987 by Society for Neuroscience
Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain
A Mansour, H Khachaturian, ME Lewis, H Akil and SJ Watson
While there is an abundance of pharmacological and biochemical evidence to
suggest the existence of multiple opioid receptors, their precise
localization within the brain is unclear. To help clarify this issue, the
present study examined the distributions of the mu, delta, and kappa opioid
receptor subtypes in the rat forebrain and midbrain using in vitro
autoradiography. Mu and delta receptors were labeled with the selective
ligands 3H-DAGO (Tyr- D-Ala-Gly-MePhe-Gly-ol), and 3H-DPDPE (D-Pen2,
D-Pen5-enkephalin), respectively, while the kappa receptors were labeled
with 3H-(-)bremazocine in the presence of unlabeled DAGO and DPDPE. Based
on previous findings in our laboratory, the labeling conditions were such
that each ligand selectively occupied approximately 75% of each of the
opioid sites. The results demonstrated that all 3 opioid receptor subtypes
were differentially distributed in the rat brain. Mu binding was dense in
anterior cingulate cortex, neocortex, amygdala, hippocampus, ventral
dentate gyrus, presubiculum, nucleus accumbens, caudate putamen, thalamus,
habenula, interpeduncular nucleus, pars compacta of the substantia nigra,
superior and inferior colliculi, and raphe nuclei. In contrast, delta
binding was restricted to only a few brain areas, including anterior
cingulate cortex, neocortex, amygdala, olfactory tubercle, nucleus
accumbens, and caudate putamen. Kappa binding, while not as widespread as
observed with mu binding, was densely distributed in the amygdala,
olfactory tubercle, nucleus accumbens, caudate putamen, medial preoptic
area, hypothalamus, median eminence, periventricular thalamus, and
interpeduncular nucleus. While all 3 opioid receptor subtypes could
sometimes be localized within the same brain area, their precise
distribution within the region often varied widely. For example, in the
caudate putamen, mu binding had a patchy distribution, while delta and
kappa sites were diffusely distributed, with delta sites being particularly
dense ventrolaterally and kappa sites being concentrated ventromedially.
These results support the existence of at least 3 distinct opioid receptors
with possibly separate functional roles.
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