The automated analysis of coordinated hindlimb movement in rats during acute and prolonged exposure to toxic agents

Abstract

The effects of CNS-active drugs and neurotoxic agents on motor coordination in the rat were studied using a newly developed, automated technique. In this test, a tv/microprocessor-based system was utilized to detect and describe the movement and placement characteristics of one of the rat's hindpaws as the rat placed its paw from one rung to another while walking in a rotating wheel. In studies employing a wheel speed of 8.2 cm/sec and a single 90-sec trial, significant deficits in coordinated hindlimb movement could be detected following the acute ip administration of a variety of compounds, including acrylamide (0, 50, and 100 mg/kg), diazepam (0, 0.5, 1.0, and 2.0 mg/kg), ethyl alcohol (0, 600, 900, and 1200 mg/kg), and tremorine (0, 2.5, 5.0, and 10.0 mg/kg). Further, results from a subacute study involving the oral administration of 2,5-hexanedione (2,5-HD; 0, 250, and 600 mg/kg) indicated that rats treated with 600 mg/kg, 2,5-HD were significantly impaired after 1 week of treatment and those treated with 250 mg/kg 2,5-HD, after 2 weeks of treatment. Although both groups improved during the recovery period, the performance of the 600 mg/kg group 5 weeks post-treatment was still inferior to controls. Taken together, these studies indicate that the coordinated hindlimb placement test provides a reliable, sensitive, and rapid technique for quantifying deficits in motor coordination in the rat during acute and prolonged exposure to neurotoxic substances.