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 lisuride, a dopamine agonist, using the 4-vessel occlusion rat model. Functional improvement was evaluated with two behavior tests exploring learning and memorization capacity in the rat, the Morris water maze and the 14-unit T-maze, 18 days after ischemia. Extracellular dopamine levels during ischemia were determined in search of a possible neuroprotection mechanism. Dopamine and its metabolites, DOPAC and HVA, as well as the serotonin metabolite, 5-HIAA, were assayed with HPLC-EC, in striatal extracellular fluid obtained by in vivo microdialysis in the awake rat. Lisuride was administered at a total dose of 10 ng by continuous intrastriatal infusion or at the dose of 0.5 mg/kg by i.p. infusion, 160 minutes before onset of ischemia for the neurochemical study and 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 showed significantly better recovery in both sets of behavioral tests, with more pronounced positive results with the 14-unit T-maze, in comparison with the saline-treated animals. Microdialysis confirmed a significant attenuation of the ischemia-induced dopamine surge, whatever the 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 in the rat; the mechanism would imply, at least in part, reduced levels of extracellular dopamine.
Caldwell
M A
MA
Department of Pharmacology, University College Galway, Ireland.
Reymann
J M
JM
Allain
H
H
Leonard
B E
BE
Bentué-Ferrer
D
D
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism* / Q000523:psychology*; D002946:Cisterna Magna; D003071:Cognition / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D007267:Injections; D007274:Injections, Intraperitoneal; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D008090:Lisuride / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018491:Dopamine Agonists; D018377:Neurotransmitter Agents; D008090:Lisuride; D004298:Dopamine