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High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time...

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Detalles Bibliográficos
Autores principales: Gerson, Julian, Erdal, Murat Kaan, McDonough, Matthew H., Ploense, Kyle L., Dauphin-Ducharme, Philippe, Honeywell, Kevin M., Leung, Kaylyn K., Arroyo-Curras, Netzahualcoyotl, Gibson, Jenny M., Emmons, Nicole A., Meiring, Wendy, Hespanha, Joao P., Plaxco, Kevin W., Kippin, Tod E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191434/
https://www.ncbi.nlm.nih.gov/pubmed/37196087
http://dx.doi.org/10.1126/sciadv.adg3254
Descripción
Sumario:Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 μM limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (±10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.