Regional central serotonin receptor binding in rats treated chronically with high-dose 5-hydroxy-L-tryptophan.

The serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (L-5-HTP) exerted differential regional effects on central 5-HT receptors in rats treated chronically by intraperitoneal injections of large incremental doses (50-200 mg/kg). There were significant reductions in Bmax of agonist-labelled (-35%) and antagonist-labelled (-20%) 5-HT2 sites in cortex but no changes in brainstem. KD and nH were unaffected by L-5-HTP. Bmax of 5-HT1 sites (unsubtyped) was reduced 16% in cortex and 18% in spinal cord, but the changes were not significant. Brainstem 5-HT1 sites were unaffected. Studies at a single isotope concentration in other regions revealed significant reductions of antagonist-labelled 5-HT2 specific binding in diencephalon (-26%) but not septum, and of 5-HT1 binding in diencephalon (-25%) and cerebellum (-30%) but not in hippocampus or striatum. Absence of L-5-HTP-evoked changes in 5-HT receptors in brainstem may have implications for L-5-HTP-responsive and brainstem-mediated human myoclonic disorders.