SIMULTANEOUS MICRODIALYSIS IN BRAIN AND BLOOD OF THE MOUSE - EXTRACELLULAR AND INTRACELLULAR BRAIN COLCHICINE DISPOSITION

A simultaneous brain and blood microdialysis system was developed to s tudy the passage of colchicine through the blood-brain barrier in the mouse. Colchicine was administered as a bolus in the jugular vein (1.5 mg kg(-1)) and its hippocampal extracellular fluid (ECF) and blood ki netics were determined over a 4 h period using two microdialysis probe s, one in the dorsal hippocampus, the other in the inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum concentrati on in the first dialysate sample) and brain and blood concentrations d eclined in parallel, suggesting rapid equilibration between these two compartments. However, only 6.7% of total blood colchicine, 14% of unb ound colchicine was present in the hippocampus suggesting that the P-g lycoprotein efflux pump limits colchicine uptake by the brain. We also found, using conventional tissue homogenate analysis in parallel, tha t the concentration of colchicine in the hippocampal ECF was 10 times less than that in the intracellular space and that the hippocampus col chicine concentration was 2.8 times higher than that of the rest of th e brain. This study shows that the simultaneous brain and blood microd ialysis can be used to measure the passage of colchicine through the b lood-brain barrier and to estimate the brain extra-and intracellular d istribution of colchicine. (C) 1998 Elsevier Science B.V.