CHANGES IN NMDAR2 SUBUNIT MESSENGER-RNA LEVELS DURING PENTOBARBITAL TOLERANCE WITHDRAWAL IN THE RAT-BRAIN - AN IN-SITU HYBRIDIZATION STUDY/

Little is known about the functional modulation of NMDA receptor subun its at the molecular level. Therefore, a series of experiments were co nducted to elucidate more fully the role of NMDA receptor subtypes in pentobarbital tolerance and withdrawal. We investigated the influence of centrally administered pentobarbital on the regulation of mRNA leve ls of the family of NMDA receptor 2 (NR2) subtypes (NR2A, NR2B, and NR 2C) by in situ hybridization histochemistry in rat brain. Animals were rendered tolerant by continuous intracerebroventricular (i.c.v.) infu sion with pentobarbital (300 mu g/10 mu l/hr for 6 days) through pre-i mplanted cannulae connected to osmotic mini-pumps, and dependent, by a brupt withdrawal from pentobarbital. The NR2A subunit mRNA was increas ed in cortical areas in pentobarbital tolerant and withdrawal rats. In contrast, the NR2B mRNA was decreased in parietal cortex and hippocam pus in both tolerance and withdrawal rats. The level of NR2C mRNA was increased in withdrawal rats, while there was no change in tolerant ra ts. These results indicate that continuous i.c.v. infusion with pentob arbital alters NR2 subunit mRNA expression in the rat brain, suggestin g that NR2 subunits may play an important role in the development of t olerance to and withdrawal from pentobarbital.