EVIDENCE FOR A PREVENTIVE ACTION OF THE VIGILANCE-PROMOTING DRUG MODAFINIL AGAINST STRIATAL ISCHEMIC-INJURY INDUCED BY ENDOTHELIN-1 IN THE RAT

We have studied the ability of the vigilance-promoting drug modafinil to counteract the ischemic lesion produced by a unilateral microinject ion of endothelin-1 (ET-1) in the neostriatum of the rat using a combi ned morphometrical, biochemical, cardiovascular and behavioral analysi s. ET-1 was injected unilaterally into the neostriatum. The ET-1-induc ed lesion volume, which was determined by a computer-assisted morphome trical analysis, was reduced by the 7-day modafinil treatment (10, 30, and 100 mg/kg i.p.) in a dose-related way. Modafinil also produced a dose-related counteraction of the ET-1-induced increase of perfusate l actate levels, as determined by intrastriatal microdialysis without af fecting the ET-1 induced reduction of striatal blood flow, as determin ed by laser-Doppler flowmetry. The ipsilateral rotational behavior ind uced by apomorphine in the ET-1-lesioned rats was reduced dose-depende ntly by modafinil treatment. Thus, morphological, neurochemical, and b ehavioral evidence that the putative ischemic striatal injury induced by microinjection of ET-1 in the rat neostriatum is counteracted in a dose-dependent way by modafinil treatment has been obtained. The mecha nism does not appear to involve an increase in striatal blood flow. It is instead speculated that its powerful preventive action in striatal ischemic injury may be related to a reduced anaerobic metabolism.