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A comparison of D1 receptor binding and mRNA in rat brain using receptor autoradiographic and in situ hybridization techniques.
- Source :
-
Neuroscience [Neuroscience] 1992; Vol. 46 (4), pp. 959-71. - Publication Year :
- 1992
-
Abstract
- D1, a subtype of the dopamine receptors, is widely distributed in the nervous system and has been shown to be positively coupled to adenylate cyclase. Using a combination of in vitro receptor autoradiographic and in situ hybridization techniques, the present study examines the co-distribution of D1 receptor binding sites and D1 receptor mRNA in adjacent rat brain sections. D1 receptor binding sites were labeled using the selective antagonist [3H](R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzaz epin- 7-ol (SCH23390) (4.6 nM), in the presence of 1 microM ketanserin, while the D1 receptor mRNA was visualized with a 35S-labeled riboprobe corresponding to a region between transmembrane domains III and VI of the rat D1 receptor (base pairs 383-843). Analysis of serial sections suggested a good agreement between D1 receptor binding and mRNA in several brain regions, including the paleocortex, caudate-putamen, nucleus accumbens, amygdala, and suprachiasmatic nucleus. Marked discrepancies between D1 receptor binding and mRNA were observed in other brain regions including the entopeduncular and subthalamic nuclei, substantia nigra (pars reticulata), hippocampus, and cerebellum. While technical considerations may contribute to these results, much of the discordance between the distributions is probably due to the differential localization of D1 receptor mRNA in cell bodies and receptor binding sites on fibers and may provide insights into receptor synthesis, transport, and membrane insertion. In the basal ganglia, for instance, D1 receptors are synthesized in the striatum and are either transported to efferent projections in areas such as the substantia nigra, or remain localized in striatal cells bodies. Ibotenic acid lesions in the striatum are consistent with these conclusions and demonstrate a coordinate loss of D1 receptor binding and mRNA in the caudate-putamen that is accompanied by a degeneration of fibers projecting to substantia nigra and a loss of D1 binding in the pars reticulata. Neurons in the dentate gyrus and in the granular layer of the cerebellum, on the other hand, synthesize D1 receptors and transport them entirely to either their dendritic or axonal fields, respectively, in the molecular layer. This analysis provides a better understanding of dopaminergic receptor systems in the CNS and their anatomical organization.
- Subjects :
- Animals
Autoradiography methods
Benzazepines metabolism
Brain drug effects
Ibotenic Acid pharmacology
Male
Nucleic Acid Hybridization
RNA Probes
RNA, Messenger analysis
RNA, Messenger genetics
Rats
Rats, Inbred Strains
Receptors, Dopamine drug effects
Receptors, Dopamine D1
Sulfur Radioisotopes
Tritium
Brain physiology
RNA, Messenger metabolism
Receptors, Dopamine genetics
Receptors, Dopamine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 46
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 1531866
- Full Text :
- https://doi.org/10.1016/0306-4522(92)90197-a