Interaction between LSD and dopamine D2/3 binding sites in pig brain
Luciano Minuzzi, George G. Nomikos, Mark Wade, Svend Borup Jensen, Aage Kristian Olsen Alstrup, Paul Cumming
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with PET imaging, in vitro binding, and microdialysis Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Pigs (for PET and in vitro), rats (for microdialysis) |
| Intervention | LSD |
| Dose | 2.5 microg/kg, i.v. |
| Duration | 4 hours post-administration |
| Topics | Serotonin LSD |
| Keywords | Raclopride Dopamine receptor d2 Pharmacology Striatum Binding potential Hallucinogen Microdialysis |
| Citations | 25 |
| Key findings | LSD reduces dopamine D2/3 receptor availability in pig striatum by 19% at 4 hours, consistent with a direct receptor interaction. |
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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 10
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
- Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study. Addiction Biology February 1, 2022
- Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Neuropsychopharmacology 2023
- Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD Psychopharmacology March 24, 2022
- Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans Molecules April 22, 2021
and 5 more in the library
Cites 12
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Diverse Psychotomimetics Act Through a Common Signaling Pathway Science November 21, 2003
- Localization of serotonin 5‐HT2 receptors in living human brain by positron emission tomography using N1‐([11C]‐methyl)‐2‐BR‐LSD Synapse 1987
- Effects of chlorimipramine and lysergic acid diethylamide on efflux of precursor-formed 3-H-serotonin: correlations with serotonergic impulse flow. Journal of Pharmacology and Experimental Therapeutics June 1, 1975
- Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain Brain Research August 1, 1975
and 7 more in the library