previously taken up by the amygdala is released along with known neurotransmitters into the extracellular space during stimulation with 100 mM KCl. The possibility of manganese release from neuron terminals in a calcium- and impulse-dependent manner was examined by using the in vivo microdialysis method in the present study. The increase of Mn-54 release into the amygdalar extracellular space during stimulation with high K+ was inhibited by addition of 1 muM tetrodotoxin. This increase of Mn-54 release into the extracellular space by stimulation with high K was also observed in the hippocampus, but not in the substantia nigra. The increment of glutamate in the extracellular space during stimulation with high K+ was highly correlated with that of Mn-54, suggesting that manganese is concurrently released with glutamate from neuron terminals. The level of Mn-54 in the extracellullar space in the hippocampus was increased with that of glutamate, but not with those of GABA and glycine, during stimulation with 100 mM KCl in the presence of 30 muM kainate. This increase was more marked than during stimulation with 30 muM kainate alone. It is likely that manganese is released from glutamatergic neuron terminals. When the rat hippocampus was perfused with artificial cerebrospinal fluid containing 20 or 200 nM MnCl2, the levels of glutamate, aspartate and GABA in the perfusate were dose-dependently decreased during perfusion with manganese. The present findings demonstrate that manganese released into the synaptic cleft may influence synaptic neurotransmission. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.