@misc{oai:repo.qst.go.jp:00071744,
 author = {永井, 裕司 and 菊池, 瑛理佳 and Walter, Lerchner and 井上, 謙一 and 大西, 新 and 金子, 博之 and 加藤, 陽子 and 堀, 由紀子 and 季, 斌 and 熊田, 勝志 and 張, 明栄 and 青木, 伊知男 and 須原, 哲也 and 高田, 昌彦 and 樋口, 真人 and リッチモンド, バリー and 南本, 敬史 and Nagai, Yuji and Kikuchi, Erika and Inoueq, Kenichi and Onishi, Arata and Kaneko, Hiroyuki and Kato, Yoko and Hori, Yukiko and Ji, Bin and Kumata, Katsushi and Ming-Rong, Zhang and Aoki, Ichio and Suhara, Tetsuya and Higuchi, Makoto and Richmond, Barry and Minamimoto, Takafumi},
 month = {Sep},
 note = {DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) are pharmacogenetic agents that, when expressed on neuronal cell membranes and activated through systemic delivery of the targeting drug, will inhibit (or excite) activity of all neurons expressing the DREADD. Using the hM4Di receptor, an inhibitory DREADD that can be activated by clozapine-n-oxide (CNO), we have been able to (1) monitor the location and intensity of receptor expression by in vivo PET-imaging, and (2) modify monkey's behavior reversibly. In our experiments, a lentiviral vector expressing the hM4Di receptor was injected into the putamen of two macaque monkeys. PET imaging using a ligand targeting the receptor showed a focal patch of high uptake at the injection site. The location matched the site of neuronal hM4Di expression identified histochemically post-mortem. Measuring uptake of the PET ligand following different CNO doses yielded to estimate the dose-occupancy relationship for binding of CNO to the hM4Di receptor. To assess the behavioral effect, an AAV vector expressing the hM4Di receptor was injected bilaterally into the ventral striatum of a monkey that had been trained to perform a reward-size task. PET imaging verified the expression of the hM4Di receptor. The monkey's performance was altered by CNO treatment in a manner similar to that seen after bilateral inactivation of the ventral striatum with muscimol in two other monkeys. Given that PET-imaging is capable of monitoring in vivo DREADD expression, the DREADD provides a novel tool to study the neural mechanism of higher brain functions in nonhuman primates and, also, contributes to the development of human therapeutic settings., 第37回⽇本神経科学⼤会},
 title = {DREADDを⽤いたサルの⾏動制御とPET⽣体内イメージング},
 year = {2014}
}