Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders.

ABSTRACT: Non-human primate (NHP) models are essential for developing and translating new treatments that target neural circuit dysfunction underlying human psychopathology. As a proof-of-concept for treating neuropsychiatric disorders, we used a NHP model of pathological anxiety to investigate the feasibility of decreasing anxiety by chemogenetically (DREADDs [designer receptors exclusively activated by designer drugs]) reducing amygdala neuronal activity. Intraoperative MRI surgery was used to infect dorsal amygdala neurons with AAV5-hSyn-HA-hM4Di in young rhesus monkeys. In vivo microPET studies with [¹¹C]-deschloroclozapine and postmortem autoradiography with [³H]-clozapine demonstrated selective hM4Di binding in the amygdala, and neuronal expression of hM4Di was confirmed

SUBMITTER: Roseboom PH 

PROVIDER: S-EPMC8636156 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature