On the basis of the evidence that vesicular zinc may be essential to the functions of the amygdala, the movement and action of actively functioning zinc in synapses in the amygdala of rats were studied using in vivo microdialysis. The increase of (65)Zn release into the amygdalar extracellular space during stimulation with high K(+) was inhibited by the addition of 1 microM tetrodotoxin. High-K(+)-induced (65)Zn release was not observed in the substantia nigra, in which zinc-containing glutamatergic neuron terminals are assumed not to exist. The amount of (65)Zn released into the amygdalar extracellular space during stimulation with high K(+) was correlated with that of glutamate. These results suggest that zinc may be concurrently released with glutamate from the neuron terminals in the amygdala and that zinc may cooperate with glutamate in excitatory neurotransmission. When the amygdala was perfused with 10 microM calcium-ethylenediamine tetraacetic acid (CaEDTA) to chelate zinc in the extracellular space, the levels of glutamate in the extracellular space were not appreciably influenced, whereas those of gamma-aminobutyric acid (GABA) were remarkably increased. It is likely that vesicular zinc modulates GABA release in the amygdala. The modulation of GABAergic neuron activity by zinc may be important for the functions of the amygdala.