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

Abstract

A recent hypothesis for the etiology of Huntingtons disease (HD) postulates that impaired mitochondrial energy production and/or the presence of reactive free radical species may lead to slow excitotoxic neuronal death. Consistent with this hypothesis, systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats produces selective striatal neuropathology mimicking that seen in HD. Such injections of 3-NP additionally produce motor changes thought to model HD, but possible cognitive changes have not been well described. The present study explores this issue. Sixteen rats underwent acquisition training and subsequent memory assessment in a Morris water maze apparatus. Training over 5 consecutive days consisted of trials 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 conducted, in which the platform was removed and the rats were allowed to swim for 2 min. Swimming patterns were tracked and recorded. The rats receiving 3-NP had impaired memory of the platform location, as represented by decreased time swimming over the platform area, fewer entries into the area, and longer latency to entering the area. These results suggest that the 3-NP rat model produces cognitive dysfunctions that parallel HD dementia.