Toxicological evaluation of the staircase test for assessing fine motor movements.
A variety of tests have been developed to study neurotoxicant-related changes in motor function. However, despite recent advances, there remains a need for simple and specific tests of fine motor movements. Accordingly, we chose to evaluate whether a method developed for measuring changes in skilled movements following motor pathway lesions in rodents would provide a sensitive, specific, and economical approach to assessing fine motor control in the toxicology laboratory. We measured skilled paw reaching using the "staircase test" developed by Montoya et al. [Prog. Brain Res. 82 (1990) 459], in which a rat retrieves food pellets by reaching down from a central platform to a series of descending steps on either side, grasping the pellets in its forepaw, and lifting them to its mouth. Staircase boxes were scaled for the body weights of young adult male (350 g) and female (250 g) Long-Evans rats. Studies were conducted using harmaline, a tremorigen; scopolamine; methyl scopolamine; and 2,4-dithiobiuret (DTB), a compound that causes muscle weakness by interfering with cholinergic transmission at the neuromuscular junction. Harmaline (0, 1.0, 3.0, and 10.0 mg/kg) reduced pellet retrieval only at a dose that also caused visible tremor. Both scopolamine (0, 0.1, 0.3, and 1.0 mg/kg) and methyl scopolamine (0, 0.104, 0.312, and 1.04 mg/kg) impaired pellet retrieval; scopolamine was more effective than methyl scopolamine. DTB (5 daily doses of 0, 0.1, 0.2, and 0.5 mg/kg) had no effect on retrieval, even when causing visible signs of weakness. These data cast doubt on the utility of this method for detecting and quantifying subtle chemical-induced changes in motor function in rats.
Neurotoxicology Division, MD B105-04, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Tracey E
TE
Samsam
Louis G
LG
Gadrinab
Philip J
PJ
Bushnell
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D009068:Movement / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors
D009498:Neurotoxins