Effects of Endogenous Agonists, Glycine and D-Serine, on In Vivo Specific Binding of [11C]L-703,717, a PET Radioligand for the Glycine-Binding Site of NMDA Receptors

A positron-emitter (carbon-11) labeled antagonist for the glycine-binding site of NMDA receptors, [11C]L-703,717, has a unique in vivo binding characteristic, in which it preferentially binds to cerebellar-specific NMDA receptors consisting of GluRe3 subunit and eventually accumulates in rodent cerebellum under in vivo conditions, but not under in vitro conditions. In order to understand the in vivo-specific site and subunit localization of this radioligand, we examined the effect of endogenous glycine site agonists, glycine and D-serine, on in vivo [11C]L-703,717 binding. An increase in extracellular glycine concentration by treatment with a glycine transporter 1 (GlyT1)-selective inhibitor, NFPS ethyl ester, significantly decreased the cerebellar localization of [11C]L-703,717 in rats. D-serine is known to be concentrated in mammalian forebrain regions. The lack of D-serine detection in the cerebellum may be due to the fact that it has the highest enzymatic activity of D-amino acid oxidase (DAO). It was found that the cerebellar localization of [11C]L-703,717 is greatly diminished in mutant mice lacking DAO, in which D-serine content in the cerebellum is drastically increased from a nondetectable level in normal mice. These studies indicate that [11C]L-703,717 is susceptible to inhibition by glycine site agonists in its in vivo binding, and suggest that regional differences in inhibitions by endogenous agonists may be a crucial factor in the site- and subunit-specific binding of this glycine-site antagonist

Chronic repetitive transcranial magnetic stimulation failed to change dopamine synthesis rate: Preliminary L-[beta-11C]DOPA positron emission tomography study in patients with depression

We have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on central dopaminergic function in patients with depression using positron emission tomography with L-[beta-11C]DOPA, a ligand to assess the rate of endogenous dopamine synthesis. Eight patients were treated with 10-daily sessions of rTMS over the left dorsolateral prefrontal cortex. Positron emission tomography scanning was performed in each patient twice, before the first session and 1 day after the last session. Although four out of eight patients responded to rTMS, there were no changes in the striatal dopamine synthesis rate (k) following rTMS. These results suggest that chronic rTMS had a limited effect on the dopaminergic system

rTMS failed to change [11C]raclopride binding in depressed patinets

8ｔｈ　world congress of biological psychiatr