ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
Chronic Behavioral Manipulation via Orally Delivered Chemogenetic Actuator in Macaques.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Chemogenetic activation of the amygdala core nucleus increases aggression in chickens.iScience · 2026Article
- Noninvasive focal gene transfer of chemogenetic proteins in the primate brain.Cell reports methods · 2026Article
- Long-term Locus Coeruleus Stimulation Exacerbates Tau Pathology in PS19 Mice.bioRxiv : the preprint server for biology · 2025Article
- Article
- GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.JCI insight · 2025Article
- G proteins of the GScience advances · 2025Article
- A humanized Gs-coupled DREADD for circuit and behavior modulation.Frontiers in cellular neuroscience · 2025Article
- What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry?Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Chemogenetic inhibition of the lateral hypothalamus effectively reduces food intake in rats in a translational proof-of-concept study.Scientific reports · 2024Article
- Imaging-based chemogenetics for dissecting neural circuits in nonhuman primates.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Review
- Targeted Delivery of Chemogenetic Adeno-Associated Viral Vectors to Cortical Sulcus Regions in Macaque Monkeys by Handheld Injections.Bio-protocol · 2023Article
- Genetic Approaches for Neural Circuits Dissection in Non-human Primates.Neuroscience bulletin · 2023Review
- Chemogenetic attenuation of cortical seizures in nonhuman primates.Nature communications · 2023Article
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- Chemogenetic activation of PVN CRH neurons disrupts the estrous cycle and LH dynamics in female mice.Frontiers in endocrinology · 2023Article
- Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats.Frontiers in neuroscience · 2023Article
- Dissecting the Prefrontal Network With Pathway-Selective Manipulation in the Macaque Brain-A Review.Frontiers in neuroscience · 2022Review
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 DREADD 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 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.