Positron Emission Tomography Studies on Some Neurotransmitter Receptor Systems with 6R-Tetrahydrobiopterin Pretreatment

Our recent microdialysis studies demonstrated the effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4, R-THBP) on the promotion of release of dopamine, serotonin, and noradrenaline1,2. In addition to this primary effect of R-THBP, glutamatergic, GABAergic, and cholinergic systems were secondarily activated via activation of such monoaminergic systems2–5. These results could explain the mechanisms of clinical efficacy of R-THBP treatment on some neuropsychiatric disorders such as infantile autism6, depression and so on. Although our microdialysis studies have been done using normal rats, the hypothesis that enhanced neurotransmitters’ release induced by R-THBP explains its therapeutic effect could be tested in the patients and by peripheral administration. Therefore, we attempted to apply the peripheral injection of R-THBP to evaluate its effect on neurotransmitter dynamics by use of positron emission tomography (PET) in human subjects and primates. Recently, we5 have demonstrated the enhancement of DOPA turnover and dopamine release in vivo by intravenous injection of R-THBP into the rhesus monkey by use of PET and 3,4-dihydroxy-L-[B-11C] phenylalanine (DOPA). To extend this result to dopamine and other neurotransmitter receptors, PET studies using various 11C-labelled receptor ligands have been performed. Here, we summarize the effects of peripheral administration of R-THBP on the dopaminergic, nicotinic and muscarinic cholinergic receptor systems.