Interaction between LSD and dopamine D2/3 binding sites in pig brain
Abstract
The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD.
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In anesthetized pigs, IV acute LSD (2.5 μg/kg) had no immediate effect on striatal [11C]-raclopride BPND, but there was a 19% decline at four hours after the challenge.
“There was no immediate effect on the striatal [11C]-raclopride (41) BPND, but there was a 19% decline at four hours after the challenge”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [98]
The 19% decline at four hours seemed consistent with a high affinity component of the displacement of [3H]-raclopride binding by LSD in pig brain sections.
“which seemed consistent with a high affinity component of the displacement of [3H]-raclopride binding by LSD (1) in pig brain sections.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [98]
Rat microdialysis studies did not indicate any effect of LSD on dopamine release per se, suggesting that the [11C]-raclopride binding reduction must be due to direct competition from LSD.
“Furthermore, their rat microdialysis studies did not indicate any effect of LSD (1) on dopamine release per se, suggesting that the [11C]-raclopride (41) binding reduction must be due to direct competition from LSD.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [98]
PET studies with [15O]-water in anesthetized pig did not indicate any effects of LSD treatment on cerebral perfusion.
“PET studies with [15O]-water in anesthetized pig did not indicate any effects of LSD (1) treatment on cerebral perfusion [98].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [98]
Cites
Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2569 · Cited by 1,154 · cited 1× · see citing works
“…been considered a possible locus of the psychopathology of schizophrenia (Carlsson, 1988; Carlsson et al., 2001) and has been further implicated on the basis of recent PET imaging studies of schizophrenia (Abi-Dargham et al., 1998; Breier et al., 1997; Laruelle et al., 1996; Reith et al., 1994).”
BackgroundTiteler, M., Lyon, R. A., & Glennon, R. A. (1988) · Psychopharmacology · doi:10.1007/bf00176847 · Cited by 343 · see citing works
Cumming, P., Wong, D. F., Gillings, N., Hilton, J., Scheffel, U., & Gjedde, A. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200205000-00011 · Cited by 71 · see citing works
Self-citationMapping the amphetamine-evoked dopamine release in the brain of the Gottingen minipig
Lind, N. M., Olsen, A. K., Moustgaard, A., Jensen, S. B., Jakobsen, S., Hansen, A. K., Arnfred, S. M., Hemmingsen, R. P., Gjedde, A., & Cumming, P. (2005) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2004.08.007 · Cited by 28 · see citing works
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Nichols, D. E. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011478 · Cited by 1,762 · see citing works
De Gregorio, D., Posa, L., Ochoa-Sanchez, R., McLaughlin, R., Maione, S., Comai, S., & Gobbi, G. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.08.022 · Cited by 110 · see citing works
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 · see citing works
“PET studies with [15O]-water in anesthetized pig did not indicate any effects of LSD (1) treatment on cerebral perfusion [98].”
MethodSelf-citationMinuzzi, L., & Cumming, P. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.01.010 · Cited by 15 · see citing works
Self-citation
- Authors
- Minuzzi, L., Nomikos, G. G., Wade, M. R., Jensen, S. B., Olsen, A. K., & Cumming, P.
- Affiliations
- Aarhus University (DK)
- Eli Lilly (United States) (US)
- Corresponding author
- Minuzzi, Luciano
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2005
- Volume
- 56
- Issue
- 4
- Pages
- 198-204
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- OpenAlex
- W1996757413
- Cited by
- 26
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 3 · 2021: 1 · 2020: 1 · 2017: 1 · 2016: 4 · 2012: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- lysergic acid diethylamide, LSD, dopamine D2/D3 receptors, [11C]raclopride, receptor binding potential, striatum, receptor displacement, hallucinogens, psychopharmacology, pig brain, cerebral blood flow
- MeSH terms
- Analysis of Variance, Animals, Autoradiography, Binding Sites, Brain, Brain Mapping, Carbon Isotopes, Dopamine, Dose-Response Relationship, Drug, Female, Homovanillic Acid, Lysergic Acid Diethylamide, Swine, Time Factors, 3,4-Dihydroxyphenylacetic Acid, Serotonin Receptor Agonists, Receptors, Dopamine D2, Microdialysis, Dopamine Antagonists, Raclopride, Positron-Emission Tomography, Receptors, Dopamine D3
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