Stereospecific binding of d-lysergic acid diethylamide (LSD) to brain membranes: Relationship to serotonin receptors

James P. Bennett, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

d-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 °C. Binding is enriched in crude microsomal (P3) membranes. d-[3H]LSD binding is stereospecific as l-LSD, the psychotropically inactive enantiomer, is 1000 times weaker than d-LSD as a displacing agent. The potencies of other LSD analogues parallel their psychotropic activity with the exception of 2-bromo-LSD (psychotropically inactive) which is as potent as d-LSD in displacing bound d-[3H]LSD. Serotonin is the only putative neurotransmitter with affinity (ED50 = 3 μM) for the LSD binding site, and psychotropically active alkylindoleamines are also potent displacing agents. Destruction of presynaptic serotonin neuronal elements by lesioning the midbrain raphe nuclei does not change the affinity or maximum number of detectable in vitro d-[3H]LSD binding sites. The regional distribution in monkey brain of d-[3H]LSD binding and high affinity [3H]serotonin uptake, a marker for pre-synaptic serotonin nerve terminal density, shows some correlation. The most notable exceptions are cerebral cortical areas which are highest in d-[3H]LSD binding and only intermediate in [3H]serotonin uptake. Our evidence suggests that d-[3H]LSD binds to post-synaptic serotonin receptors.

Original languageEnglish (US)
Pages (from-to)523-544
Number of pages22
JournalBrain research
Volume94
Issue number3
DOIs
StatePublished - Sep 5 1975

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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