High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats
Julian Gerson, Murat Kaan Erdal, Matthew H. McDonough, Kyle L. Ploense, Philippe Dauphin‐Ducharme, Kevin M. Honeywell, Kaylyn K. Leung, Netzahualcóyotl Arroyo‐Currás, J. M. Gibson, Nicole Emmons, Wendy Meiring, João P. Hespanha, Kevin W. Plaxco, Tod E. Kippin
Abstract
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.