Effects of GABA and glutamate antagonists as well as dopamine agonists and antagonists on the optical responses of neostriatal (Str) slices to local electrical stimulation were examined using a voltage-sensitive dye and a high-speed image sensor. A single local stimulation applied to the Str slices evoked optical responses lasting for 40-80 ms and propagating in every direction up to about 1.5 mm. Bath application of bicuculline methiodide increased the intensity and duration of optical responses, while their spatial response patterns were unchanged. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) greatly reduced the late part of responses occurring about 4 ms after stimulation, but the early part of responses was unaffected by CNQX. The early part of the response was eliminated by application of tetrodotoxin. Bath application of N-methyl-D-aspartate antagonists, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid resulted in only small changes in the optical responses. Bath application of D1 agonist 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benz aze pine hydrobromide consistently increased the intensity but decreased the speed of propagation and duration of the optical response. Bath application of D2 agonist quinpirole had no effect on the optical response. D1 antagonist SCH 23390 and D2 antagonist sulpiride also failed to change optical responses. These results indicate that the early part of the response is due to direct activation of the neuronal elements by electrical stimulation, while the late part of the response is due mainly to glutamatergic ex-citatory postsynaptic potentials (EPSPs) mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors. This study also suggests that dopamine may modulate AMPA/kainate responses through D1 receptors.