MITOCHONDRIAL TOXIN 3-NITROPROPIONIC ACID PRODUCES STARTLE REFLEX ABNORMALITIES AND STRIATAL DAMAGE IN RATS THAT MODEL SOME FEATURES OF HUNTINGTONS-DISEASE

Systemic administration of the mitochondrial toxin 3-nitropropionic ac id (3NP) to rats produces striatal lesions that mimic some aspects of pathology in Huntington's disease (HD). To evaluate whether 3NP-induce d lesions cause sensorimotor gating deficits observed in HD, we measur ed prepulse inhibition (PPI) of the acoustic startle reflex after syst emic administration of 3NP (10, 15, or 20 mg/kg) to 5-month-old rats. PPI, the reduction of startle magnitude by a weak auditory prestimulus , is significantly reduced in patients with HD. Two daily injections o f 3NP produced gross histologic evidence of striatal lesions in some r ats and significantly reduced PPI. Striatal lesions also significantly disrupted amphetamine-induced stereotypy, another index of dorsal str iatal function. 3NP thus reproduces a specific objective and quantifia ble gating deficit found in patients with HD. (C) 1997 Elsevier Scienc e Ireland Ltd.