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Localization and characterization by quantitative autoradiography of [125I]LSD binding sites in rat brain
Abstract
The binding of [125I]LSD in rat brain was characterized and localized by quantitative autoradiography. Frozen 32 microns thick brain sections were labeled in vitro with [125I]LSD and exposed for 24 h against LKB Ultrofilm to generate autoradiograms. Nonspecific binding was defined as the labelling in the presence of 1 microM D-LSD. Scatchard analysis by densitometry indicated that the binding of [125I]LSD was saturable, with a Kd of 0.2 nM. In agreement with the results of Hartig and co-workers [5,6], [125I]LSD showed a high affinity for 5-HT2 serotonin receptors with some overlap with D-2 dopamine receptors. High concentrations of [125I]LSD sites were observed in layer IV of the cerebral cortex, caudate-putamen, claustrum, olfactory tubercle, nucleus accumbens, ependyma, mammillary nucleus and inferior olive. Co-incubation of sections with sulpiride to block binding to D-2 receptors resulted in a uniform 20-30% reduction in the amount of specific [125I]LSD binding, with no qualitative difference in the pattern of labeling. However, co-incubation with ketanserin to block 5-HT2 receptors resulted in a pattern of binding that was similar to previous descriptions of the location of D-2 receptors, with high levels of residual binding in caudate-putamen, olfactory tubercle, nucleus accumbens and inferior olive. Our results indicate that [125I]LSD is a suitable ligand for quantitative autoradiography of both 5-HT2 and D-2 receptors, and that there is a strong anatomical correspondence between these receptor subtypes, perhaps implying a functional interaction.
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D-[125I]-LSD binding in rat brain indicated a single population of binding sites (KD 170 pM) in cerebral cortex, with Bmax about 4 pmol/g wet weight.
“More detailed autoradiographic examination of D-[125I]-LSD (25) binding in rat brain indicated a single population of binding sites (KD 170 pM) in cerebral cortex, where the Bmax was about 4 pmol/g wet weight [73].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [73]
Binding in striatum was of similar density but with a higher apparent KD (300 pM), indicative of slightly lower affinity of LSD for dopamine D2-like receptors.
“The binding in striatum was of similar density, but with a higher apparent KD (300 pM), indicative of the slightly lower affinity of LSD (1) for dopamine D2-like receptors.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [73]
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Research works printed but not linked: 13
- Alexander, 1981, Quantitative measurement of local cerebral metabolic rate for glucose utilizing tritiated 2-deoxyglucose, Brain Res., 223, 59, 10.1016/0006-8993(81)90806-4 · DOI
- Altar, 1983, [3H]spiroperidol binding to rat forebrain sections. 2. Computer-assisted image processing, Soc. Neurosci. Abstr., 9, 1113
- Battaglia, 1983, Hallucinogenic drug interactions with S-1 and S-2 cortical serotonin receptors, Soc. Neurosci. Abstr., 9, 1157
- Creese, 1976, Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs, Science, 192, 481, 10.1126/science.3854 · DOI · Paper page
- Hartig, 1983, [125I]LSD: a high sensitivity ligand for serotonin receptors, Europ. J. Pharmacol., 89, 321, 10.1016/0014-2999(83)90515-0 · DOI
- Hartig, 1983, [125I]LSD: a selective, high-sensitivity ligand for serotonin 5HT-2 receptors, Soc. Neurosci. Abstr., 9, 334
- Herkenham, 1983, Quantification of receptor densities by autoradiography: tissue defatting minimizes differential absorbance of tritium by grey and white matter, Soc. Neurosci. Abstr., 9, 329
- Krieg, 1946, Connections of the cerebral cortex. I. The albino rat: a topography of the cortical areas, J. comp. Neurol., 84, 221, 10.1002/cne.900840205 · DOI
- Leysen, 1983, Role and localization of serotonin-2 (S-2) receptor binding sites: effects of neuronal lesions, Advanc. Biochem. Psychopharmacol., 37, 373
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Nichols, D. E. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2003.11.002 · Cited by 1,211
Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans.
Cumming, P., Scheidegger, M., Dornbierer, D., Palner, M., Quednow, B. B., & Martin-Soelch, C. (2021) · Molecules · doi:10.3390/molecules26092451 · Cited by 43
“More detailed autoradiographic examination of D-[125I]-LSD (25) binding in rat brain indicated a single population of binding sites (KD 170 pM) in cerebral cortex, where the Bmax was about 4 pmol/g wet weight [73].”
Background
Metadata
- Authors
- Nakada, M. T., Wieczorek, C. M., & Rainbow, T. C.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Rainbow, Thomas C.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1984-08
- Volume
- 49
- Issue
- 1-2
- Pages
- 13-18
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1988375361
- Cited by
- 38
- References
- 0
- Citations by year
- 2025: 2 · 2023: 1 · 2021: 1 · 2018: 1 · 2017: 1 · 2012: 1
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- 5-HT2 receptor, dopamine D2 receptor, receptor localization, receptor binding affinity, sulpiride, ketanserin, receptor colocalization, rat brain, caudate-putamen, nucleus accumbens, olfactory tubercle, inferior olive
- MeSH terms
- Animals, Basal Ganglia, Binding Sites, Brain, Caudate Nucleus, Cerebral Cortex, Lysergic Acid Diethylamide, Olfactory Bulb, Putamen, Receptors, Dopamine, Receptors, Serotonin, Rats, In Vitro Techniques
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