Mitochondrial toxin 3-nitropropionic acid produces startle reflex abnormalities and striatal damage in rats that model some features of Huntington's disease.
Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP) to rats produces striatal lesions that mimic some aspects of pathology in Huntington's disease (HD). To evaluate whether 3NP-induced lesions cause sensorimotor gating deficits observed in HD, we measured prepulse inhibition (PPI) of the acoustic startle reflex after systemic 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 of 3NP produced gross histologic evidence of striatal lesions in some rats and significantly reduced PPI. Striatal lesions also significantly disrupted amphetamine-induced stereotypy, another index of dorsal striatal function. 3NP thus reproduces a specific objective and quantifiable gating deficit found in patients with HD.
Kodsi
M H
MH
Department of Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804, USA.
Swerdlow
N R
NR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D000959:Antihypertensive Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid