Autoradiography of [H-3]glutamate binding during pentobarbital tolerance and withdrawal in the rat

The influence of centrally administered pentobarbital on [H-3]glutamate rec eptor binding in the rat brain was examined. Animals were rendered tolerant by intracerebroventricular (i.c.v.) infusion through osmotic minipumps wit h pentobarbital (300 mu g/10 mu l/h, for 6 days) and dependent, by 24 h aft er withdrawal from pentobarbital. Pentobarbital tolerant rats have signific ant increases in [H-3]glutamate binding in the cortex and hippocampus area. Pentobarbital withdrawal produced increases in glutamate binding in many r egions, e.g., the cortex, hippocampus area, thalamus, and cerebellum. These results show that chronic i.c.v. infusion with pentobarbital increases N-m ethyl-D-aspartate (NMDA) displaceable [H-3]glutamate binding, suggesting th at an increase in NMDA binding sites may play an important role in the deve lopment of tolerance to and withdrawal from pentobarbital. (C) 1999 Elsevie r Science Inc.