Systemic 3-nitropropionic acid: Behavioral deficits and striatal damage in adult rats

Previous animal studies have demonstrated that systemic administration of 3-nitropropfonic acid 3-NP) leads to neuropathological changes similar to those seen in Huntington's disease (HD). Recently, we reported hypeactivity in 6- and 10-week old rats treated with systemic 3-NP OP, 10 mg/kg/day) once every 4 days for 28 days. Although these behavioral results seem to differ from the observed hyperactivity in most excitotoxic models of HD, 3-NP may provide a better model of juvenile onset and advanced HD. In the present study, older rate were similarly treated with 3-NP to further characterize the reported age dependency of striatai neuronal death caused by 3-NP. Hypoactivtty was observed In 14- and 28-week old rats with the latter demonstrating more profound features. The present study also provided the first direct evidence of a 3-NP affect on passive avoidance behavior. Experimental and control animals showed no sigraficant difference in daytime acquisition and retention of a passive avoidance task. However, when the retention tests were conducted during the night time (in contrast to previous daytime tests), 3-NP-treated animals exhibited significant retention deficits. M addition, the neuropathological effects of 3-NP were determined by Nissi, ACNE and NADPH-diaphorase histochemistry. Metabolic activity was studied using cytochroms oxidase activity as an index. Results revealed striatal glial infiltration, lose of intrinsic striatai Cholingergic neurons, but some sparing of large ACNE positive neurons, minimal damage of NADPH-disphorase-containing neurone, and very slight, if any, alterations in cytochrome oxidese activity. In summary, the present results revealed that long-term systemic administration of 3-NP leads to a) an age-dependent hypoactivity, b) a contextual retention deficit in paasive avoidance, and c) a selective destruction of striatal neuronal populations.