Interaction between LSD and dopamine D2/3 binding sites in pig brain
Synapse – January 01, 2005
Source: OpenAlex
Summary
LSD significantly impacts dopamine D2/3 receptor availability, evidenced by a 19% reduction in binding potential in the striatum four hours post-administration in a study involving three pigs. Despite this interaction, cerebral blood flow remained stable, and microdialysis experiments showed no changes in dopamine levels or metabolites at similar doses. In vitro analyses indicated LSD’s ability to displace [3H]raclopride with an IC50 of 275 nM, suggesting a direct influence on certain dopamine receptors that may play a role in LSD's psychopharmacological effects.
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.