Rats receiving systemic 3-nitropropionic acid demonstrate impairment of memory in Morris water maze

A recent hypothesis for the etiology of Huntington's disease (HD) postulate s that impaired mitochondrial energy production and/or the presence of reac tive free radical species may lead to slow excitotoxic neuronal death. Cons istent with this hypothesis, systemic administration of the mitochondrial t oxin 3-nitropropionic acid (3-NP) in rats produces selective striatal neuro pathology mimicking that seen in HD. Such injections of 3-NP additionally p roduce motor changes thought to model HD, but possible cognitive changes ha ve not been well described. The present study explores this issue. Sixteen rats underwent acquisition training and subsequent memory assessment in a M orris water maze apparatus. Training over 5 consecutive days consisted of t rials during which each rat could escape swimming by finding a permanently located submerged platform. Following training, the rats were divided into two groups and received daily intraperitoneal injections of either 3-NP (15 mg/kg) or saline vehicle for 7 days. On Day 8, a retention trial was condu cted, in which the platform was removed and the rats were allowed to swim f or 2 min. Swimming patterns were tracked and recorded. The rats receiving 3 -NP had impaired memory of the platform location, as represented by decreas ed time swimming over the platform area, fewer entries into the area, and l onger latency to entering the area. These results suggest that the 3-NP rat model produces cognitive dysfunctions that parallel HD dementia.