Time course and effective spread of lidocaine and tetrodotoxin delivered via microdialysis: an electrophysiological study in cerebral cortex

Microdialysis is a useful tool for administering drugs into localized regio ns of brain tissue, but the diffusion of drugs from the probe has not been systematically examined. Lidocaine (10%) and tetrodotoxin (TTX, 10 muM), dr ugs typically used in neural inactivation studies, were infused through a m icrodialysis probe into raccoon somatosensory cortex while evoked responses were recorded at four electrodes equally spaced 0.5-2.0 mm from the probe. The decreases in evoked response amplitude as a function of time and dista nce from the probe were used as functional measures to describe the time co urse and spread of the drugs. TTX inactivated distant sites more quickly an d to a greater extent than lidocaine. Responses recovered within approximat ely 40 min after termination of lidocaine, but did not recover for at least 2 h after TTX. Based on these measurements, we estimated that, at the conc entrations used, lidocaine has a maximal spread of 2.1 mm, while TTX could spread as far as 4.8 mm from the microdialysis probe. However, in terms of significant inactivation of neuronal activity, lidocaine and TTX have an ef fective spread of 1 and 2 mm, respectively. (C) 2001 Elsevier Science B.V. All rights reserved.