DOPAMINE HAS INHIBITORY AND ACCELERATING EFFECTS ON ISCHEMIA-INDUCED NEURONAL CELL-DAMAGE IN THE RAT STRIATUM

Dopaminergic (DAergic) influence on ischemic neuronal cell damage in t he dorsolateral striatum was studied. Intact and 6-hydroxydopamine (6- OHDA) lesioned rats, with and without pretreatment by D1 and D2 DA ant agonists, were subjected to 20 min forebrain ischemia. Extracellular D A and glutamate (Glu) were measured using microdialysis technique. His tological examination was performed on the dorsolateral striatum and t he hippocampal CA1 area 24 h after ischemia. DA increased 400-500 time s the control level during ischemia among the groups except the 6-OHDA lesioned group. No significant changes were observed in the concentra tion of 3,4-dihydroxyphenylacetic acid (DOPAC), but a transient decrea se was seen in homovanillic acid (HVA). Due to ischemia, Glu increased up to about 5 times the control level among the groups. Neuronal dama ge in the dorsolateral striatum was slightly attenuated by 6-OHDA lesi on. Treatment by spiperone (D2 antagonist, 7 mug/kg IP) alone attenuat ed the damage strongly. Treatment by SCH23390 (D1 antagonist, 2.5 mg/k g IP) alone or both D1 and D2 antagonists had no effects. Data suggest that excessive Glu and DA are involved in neuronal cell damage. DA mi ght enhance the damage via D2 but inhibit via D1 receptor.