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Chronic behavioral manipulation via orally delivered chemogenetic actuator in macaques
https://repo.qst.go.jp/records/85689
https://repo.qst.go.jp/records/856897822c1e0-ea03-4138-8ae7-4bce951fce6c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-02-21 | |||||
| タイトル | ||||||
| タイトル | Chronic behavioral manipulation via orally delivered chemogenetic actuator in macaques | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Kei, Oyama
× Kei, Oyama× Yukiko, Hori× Yuji, Nagai× Naohisa, Miyakawa× Koki, Mimura× Toshiyuki, Hirabayashi× Ken-ichi, Inoue× Takada, Masahiko× Makoto, Higuchi× Takafumi, Minamimoto× Kei, Oyama× Yukiko, Hori× Yuji, Nagai× Naohisa, Miyakawa× Koki, Mimura× Toshiyuki, Hirabayashi× Makoto, Higuchi× Takafumi, Minamimoto |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The chemogenetic technology referred to as designer receptors exclusively activated by designer drugs (DREADDs) offers reversible means to control neuronal activity for investigating its functional correlation with behavioral action. Deschloroclozapine (DCZ), a recently-developed highly potent and selective DREADDs actuator, displays a capacity to expand the utility of DREADDs for chronic manipulation without side-effects in nonhuman primates, which has not yet been validated. Here we investigated the pharmacokinetics and behavioral effects of orally administered DCZ in female and male macaque monkeys. Pharmacokinetic analysis and positron emission tomography (PET) occupancy examination demonstrated that oral administration of DCZ yielded slower and prolonged kinetics, and that its bioavailability was 10-20% of that in the case of systemic injection. Oral DCZ (300-1000 μg/kg) induced significant working memory impairments for at least 4 h in monkeys with hM4Di expressed in the dorsolateral prefrontal cortex (Brodmann’s area 46). Repeated daily oral doses of DCZ consistently caused similar impairments over two weeks without discernible desensitization. Our results indicate that orally delivered DCZ affords a less invasive strategy for chronic but reversible chemogenetic manipulation of neuronal activity in nonhuman primates, and this has potential for clinical application. | |||||
| 書誌情報 |
Journal of Neuroscience 巻 42, 号 12, p. 2552-2561, 発行日 2022-02 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0270-6474 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 35110390 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1523/JNEUROSCI.1657-21.2021 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.jneurosci.org/content/early/2022/02/02/JNEUROSCI.1657-21.2021.long | |||||
