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The effect of ischemia on catecholamine and 5-hydroxytryptamine (5-HT) levels in brain cortex was examined in the gerbil stroke model. Unilateral common carotid artery occlusion produced bilateral decrease in cortical dopamine levels in gerbils both symptomatic and asymptomatic of cerbral ischemia. The 5-HT progressively decreased only in the occluded hemisphere of ischemic animals. In p-chlorophenylalanine (PCPA)-treated gerbisl, dopamine decreased only in the occluded hemisphere of symptomatic animals, but norepinephrine became decreased bilaterally compared with controls. The 5-HT decrease was twice that seen in untreated animals. It is suggested that these results indicate initial release together with reduced synthesis of monoamines in ischemic brain. The incidence of ischemia induced by carotid occlusion decreased from 44% to 26% in PCPA-treated animals, which also suggests that depletion of 5-HT available for neuronal release prior to the induction of ischemia may reduce stroke incidence by limiting impairment of collateral vasocapacitance. PCPA pretreatment did not influence the development of edema in the occluded hemisphere of ischemic animals once ischemia was established.