The effects of chlormethiazole on single unit activity in rat brain; interactions with inhibitory and excitatory...

Extracellular recordings were made of single unit activity in the brainstem of urethane anaesthetized rats. Drugs were applied by microiontophoresis from multibarrelled micropipettes or administered intraperitoneally. Chlormethiazole (CMZ) caused a decrease in spontaneous firing rate when applied with high currents (greater than 40 nA). When applied with lower currents CMZ did not cause changes in firing rate, but enhanced the inhibitory effects of gamma-aminobutyric acid (GABA), muscimol and glycine in a dose-dependent manner. The inhibitory actions of acetylcholine were not affected. Excitatory responses to glutamate and acetylcholine were unaffected by applications of CMZ which caused potentiation of GABA, muscimol and glycine. When applied at higher currents CMZ caused a decrease in the response to glutamate. Intraperitoneal administration of CMZ (50-600 mumol kg-1) also enhanced responses to microiontophoretically applied GABA, muscimol and glycine. These results are compared with those reported for other anticonvulsant drugs and possible mechanisms of action of CMZ are discussed.