Effects of pentobarbital on the regulation of acetylcholine content and release in different regions of rat brain

Pentobarbital administered to rats in rivo increased the levels of acetylcholine (ACh) in the cerebral cortex, striatum, hippocampus and pons-medulla but not in the midbrain or cerebellum. It has been suggested that the increased levels of ACh may be the result of an inhibition of release of the transmitter. However, when pentobarbital was tested in vitro , it inhibited potassium-stimulated ACh release from all regions. Release of ACh and tissue levels of ACh were compared directly in cerebral cortex and midbrain in vitro . Stimulation with 25 and 50 mM KC1 enhanced ACh release from both regions but decreased tissue ACh only in the cerebral cortex. Pentobarbital inhibited potassium-stimulated ACh release from both regions but only increased tissue ACh in the cerebral cortex (stimulated with 25 mM KCl). These results suggest that the regulation of ACh synthesis and release is different in the two brain regions and that pentobarbital can inhibit ACh release without necessarily causing a concomitant rise in ACh tissue levels.