MK801 prevents quinolinic acid-induced behavioral deficits and neurotoxicity in the striatum.

Bilateral intrastriatal injections of quinolinic acid (QA) (180 nmoles) induced weight loss and neurologic and behavioral deficits including convulsions, decreased catalepsy response to haloperidol, increased nocturnal locomotor activity, and abnormal feeding behavior in adult male Sprague-Dawley rats. Pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK801 (4 mg/kg IP) 30 min prior to stereotaxic surgery prevented the appearance of all QA-induced behavioral abnormalities and prevented weight loss. Twelve weeks after surgery the QA-lesioned animals recovered to sham levels on feeding behavior and nocturnal locomotor activity, but showed persistent reductions in haloperidol-induced catalepsy. Histological examination of the QA-lesioned brains showed extensive lesions of the dorsolateral striatum and frontoparietal cortex. MK801 pretreatment protected against these lesions. These results confirm that MK801 treatment prevents the appearance of neuropathological damage after QA neurotoxicity, and further show that neuronal protection with MK801 is correlated with the absence of QA-induced behavioral deficits.