Systemic 3-nitropropionic acid: long-term effects on locomotor behavior

Abstract

Systemic administration of 3-nitropropionic acid (3-NP) results in striatal atrophy by irreversibly inhibiting the citric acid cycle, and thereby resulting in cellular ATP depletion. The neuropathological outcome following 3-NP injections is thought to resemble that seen in Huntington's disease (HD) [1]. The current study administered systemic injections in 6- and 10-week-old rats of low-dose 3-NP every other 4 days for a period of 28 days in order to investigate the effects on locomotor behavior and striatal D1 dopamine receptor binding. Experimental and control animals received intraperitoneal injections of 3-NP (10 mg/kg in 0.9% saline) and 0.9% saline, respectively. Animals were tested behaviorally prior to the first and after the last 3-NP administration. Brains were then removed and striatal tissue samples were analyzed for D1 dopamine receptor binding using [3H]SCH23390. Behaviorally, 6-week-old injected animals developed bradykinesia with no signs of stiffness or rigidity, while 10-week-old injected animals displayed an uncoordinated gait, stiffness and ventral recumbency with hind limbs extended in a rigid or fixed position. These visual observations of hypoactivity were supported by a significant decline in both experimental groups' locomotor activity as measured by Digiscan monitors. Furthermore, [3H]SCH23390 specific binding to D1 dopamine receptors revealed a small but significant decrease in 10-week-old injected animals compared to controls. These results demonstrate that both 6- and 10-week-old rats do exhibit behavioral alterations after long-term 3-NP administration, however the former may not show accompanying gross D1 receptor changes.