In vivo binding of 125I-LSD to serotonin 5-HT2 receptors in mouse brain

The binding of ¹²⁵I-LSD (2-[¹²⁵I]-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous infection of the radioligand. The high specific activity of ¹²⁵I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of ¹²⁵I-LSD binding were found in the frontal cortex, olfactory tubercles, extra- frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of ¹²⁵I-LSD. Serotonergic compounds potently inhibited ¹²⁵I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies we conclude that ¹²⁵I-LSD labels serotonin 5-HT₂ receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, ¹²⁵I-LSD labelling occurs predominantly or entirely at serotonin 5-HT₂ sites. In the striatum, ¹²⁵I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. This data indicates that ¹²⁵I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT₂ receptors in the mammalian cortex.