LISURIDE PREVENTS LEARNING AND MEMORY IMPAIRMENT AND ATTENUATES THE INCREASE IN EXTRACELLULAR DOPAMINE-INDUCED BY TRANSIENT GLOBAL CEREBRAL-ISCHEMIA IN RATS

In this experiment, we tested the efficacy of neuroprotection with lis uride, a dopamine agonist, using the 4-vessel occlusion rat model. Fun ctional improvement was evaluated with two behavior tests exploring le arning and memorization capacity in the rat, the Morris water maze and the 14-unit T-maze, 18 days after ischemia, Extracellular dopamine le vels during ischemia were determined in search of a possible neuroprot ection mechanism. Dopamine and its metabolites, DOPAC and HVA, as well as the serotonin metabolite, 5-HIAA, were assayed with HPLC-EC, in st riatal extracellular fluid obtained by in vivo microdialysis in the aw ake rat. Lisuride was administered at a total dose of 10 ng by continu ous intrastriatal infusion or at the dose of 0.5 mg/kg by i.p. infusio n, 160 minutes before onset of ischemia for the neurochemical study an d at the dose of 0.5 mg/kg via i.p. infusion, 1 hour before occlusion of the carotid arteries, for the behavior tests, Behavioral testing sh owed significantly better recovery in both sets of behavioral tests, w ith more pronounced positive results with the 14-unit T-maze, in compa rison with the saline-treated animals. Microdialysis confirmed a signi ficant attenuation of the ischemia-induced dopamine surge, whatever th e mode of administration, compared with saline-treated animals. These results show that lisuride offers significant neuroprotection from the effect of experimental transient global forebrain cerebral ischemia i n the rat; the mechanism would imply, at least in part, reduced levels of extracellular dopamine. (C) 1997 Elsevier Science B.V.