Abstract
Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the mu, delta, and kappa opioid receptors of rat brain. The mu receptors are most densely localized in patches in the striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, delta receptors are highly confined, exhibiting selective localization in layers I, II, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. delta receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the delta receptor, occur essentially throughout the brain. The kappa receptors of rat brain exhibit a third pattern distinct from that of the mu and delta receptors. kappa receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions. kappa receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer III, which revealed only trace levels of binding. An important conclusion of the present study is that delta receptors occur at high density only in the forebrain and in two midbrain structures, whereas mu and kappa receptors exhibit discrete patterns in most major brain regions.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Geary W. A., 2nd, Wooten G. F. Regional tritium quenching in quantitative autoradiography of the central nervous system. Brain Res. 1985 Jun 17;336(2):334–336. doi: 10.1016/0006-8993(85)90662-6. [DOI] [PubMed] [Google Scholar]
- Goodman R. R., Snyder S. H. Kappa opiate receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5703–5707. doi: 10.1073/pnas.79.18.5703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodman R. R., Snyder S. H., Kuhar M. J., Young W. S., 3rd Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6239–6243. doi: 10.1073/pnas.77.10.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Handa B. K., Land A. C., Lord J. A., Morgan B. A., Rance M. J., Smith C. F. Analogues of beta-LPH61-64 possessing selective agonist activity at mu-opiate receptors. Eur J Pharmacol. 1981 Apr 9;70(4):531–540. doi: 10.1016/0014-2999(81)90364-2. [DOI] [PubMed] [Google Scholar]
- Herkenham M., Pert C. B. In vitro autoradiography of opiate receptors in rat brain suggests loci of "opiatergic" pathways. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5532–5536. doi: 10.1073/pnas.77.9.5532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herkenham M., Pert C. B. Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality. J Neurosci. 1982 Aug;2(8):1129–1149. doi: 10.1523/JNEUROSCI.02-08-01129.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khachaturian H., Lewis M. E., Watson S. J. Enkephalin systems in diencephalon and brainstem of the rat. J Comp Neurol. 1983 Nov 1;220(3):310–320. doi: 10.1002/cne.902200305. [DOI] [PubMed] [Google Scholar]
- Mosberg H. I., Hurst R., Hruby V. J., Gee K., Yamamura H. I., Galligan J. J., Burks T. F. Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5871–5874. doi: 10.1073/pnas.80.19.5871. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Snyder S. H. Drug and neurotransmitter receptors in the brain. Science. 1984 Apr 6;224(4644):22–31. doi: 10.1126/science.6322304. [DOI] [PubMed] [Google Scholar]
- Tempel A., Gardner E. L., Zukin R. S. Visualization of opiate receptor upregulation by light microscopy autoradiography. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3893–3897. doi: 10.1073/pnas.81.12.3893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young W. S., 3rd, Kuhar M. J. A new method for receptor autoradiography: [3H]opioid receptors in rat brain. Brain Res. 1979 Dec 28;179(2):255–270. doi: 10.1016/0006-8993(79)90442-6. [DOI] [PubMed] [Google Scholar]
- Zukin R. S., Maneckjee R. Solubilization and characterization of opiate receptors. Methods Enzymol. 1986;124:172–190. doi: 10.1016/0076-6879(86)24015-x. [DOI] [PubMed] [Google Scholar]
- Zukin S. R., Tempel A., Gardner E. L., Zukin R. S. Interaction of [3H](-)-SKF-10,047 with brain sigma receptors: characterization and autoradiographic visualization. J Neurochem. 1986 Apr;46(4):1032–1041. doi: 10.1111/j.1471-4159.1986.tb00614.x. [DOI] [PubMed] [Google Scholar]