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
Synapse January 1, 2005 DOI: 10.1002/syn.20141 via OpenAlex
Summary
AI-generated from the abstractLSD reduces the binding potential of a dopamine D2/3 receptor tracer in the striatum of pigs, suggesting a direct interaction with these receptors. In a PET study, the binding potential of [11C]raclopride decreased by 19% four hours after LSD administration, without changes in cerebral blood flow. In vitro experiments showed LSD displaces the tracer from pig brain tissue with an IC50 of 275 nM, and a two-site model indicated a subnanomolar component comprising 20% of binding. Microdialysis in rats found no changes in dopamine or its metabolites. These findings indicate LSD directly occupies a portion of dopamine D2/3 receptors, which may contribute to its psychoactive effects.
Study at a glance
| 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) |
| Topics | Serotonin |
| Keywords | Raclopride Chemistry Dopamine receptor d2 Pharmacology Striatum |
| Citations | 25 |
| Key finding | 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.