Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin alters the binding activities of 5-HT1A and 5-HT2 receptors in rat brain.

Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) induced significant changes in the binding activities of serotonergic receptors in the rat brain. The increase in the hippocampus and the decrease in the visual cortex of [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT) binding (5-HT1A binding site) were found to be significant following R-THBP administration (20 mg/kg, twice a day for 1 week). [3H]Ketanserin binding (5-HT2 binding site) was increased in the striatum and hippocampus, whereas it was decreased in the cerebellum and visual cortex. Scatchard plot analysis showed ca. 20% reduction in the Bmax of [3H]8-OH-DPAT and [3H]ketanserin binding in the visual cortex, and KD values for [3H]8-OH-DPAT and [3H]ketanserin bindings in the hippocampus were significantly reduced 51% and 66%, respectively. These differential changes in 5-HT binding might be involved in the central action of R-THBP.