AUTORADIOGRAPHIC ESTIMATION OF THE EXTENT OF REVERSIBLE INACTIVATION PRODUCED BY MICROINJECTION OF LIDOCAINE AND MUSCIMOL IN THE RAT

We used autoradiography to examine the extent of reversible inactivation produced by microinjection of lidocaine (40-mu-g/mu-l saline) and muscimol (1-mu-g/mu-l saline). We measured intracortical spread of tracer amounts of labelled drug and local changes in uptake of [1-C-14]glucose produced by the microinjection. The maximal average radii of regions of drug spread were 1.7 mm for both [C-14]lidocaine and [H-3]muscimol and were achieved within the first 20 min postinjection. The width of lidocaine injections decreased at longer postinjection times (30-60 min) but the width of muscimol injections remained relatively constant (30-120 min). Lidocaine radioactivity decreased faster from the injection site than muscimol radioactivity. Glucose autoradiograms showed a discrete region of maximally reduced glucose uptake (1.4 mm for lidocaine and 1.0 mm for muscimol) surrounded by a region of less reduced glucose uptake (up to approximately 3 mm). These findings suggest that, in the cortex, the effects of focal inactivation extend beyond the region of drug spread. Diffuse effects may be mediated of disfacilitation of cortico-cortical circuits.