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

D-LSD binds to rat brain membranes with high affinity and stereospecificity; the psychotropically inactive L-LSD is 1000 times weaker. 2-bromo-LSD, though psychotropically inactive, displaces D-LSD as potently as D-LSD. Serotonin is the only neurotransmitter with affinity for the LSD binding site. Destroying presynaptic serotonin neurons does not alter LSD binding, suggesting the binding site is post-synaptic. Regional distribution in monkey brain shows LSD binding correlates partly with serotonin uptake, but cortical areas are highest in binding and only intermediate in uptake.

Study at a glance

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 degrees C. Binding is enriched in crude microsomal (P3) membranes. D-[3H]LSD binding is stereospecific as L-LSD, the psychotropically inactive enatiomer, 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 muM) 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 chang the affinity or maximum number of detectable in vitro D-[3H]LSD bindind 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.