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Interaction between LSD and dopamine D 2/3 binding sites in pig brain
Author(s) -
Minuzzi Luciano,
Nomikos George G.,
Wade Mark R.,
Jensen Svend B.,
Olsen Aage K.,
Cumming Paul
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20141
Subject(s) - raclopride , dopamine , chemistry , dopamine receptor d2 , pharmacology , striatum , binding potential , serotonin , hallucinogen , microdialysis , dopamine receptor , receptor , neuroscience , medicine , psychology , biochemistry
The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT 2 receptors in brain. Possible effects of LSD on dopamine D 2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential ( pB ) of [ 11 C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 μg/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 [ 3 H]raclopride (2 nM) from pig brain cryostat sections with an IC 50 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 IC 50 , comprising ˜20% of the total [ 3 H]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 D 2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. Synapse 56:198–204, 2005. © 2005 Wiley‐Liss, Inc.