Large-Scale Assessment of Motor Activity in Rodents: Procedures for Routine Use in Toxicology Studies

Abstract

An automated system for the routine large-scale assessment of motor activity in rats has been established in this laboratory for use in toxicity testing. This study was designed to evaluate the validity and sensitivity of motor activity measurements for routine use in toxicology studies. The effects of two known neurotoxins, acrylamide (ACR) and 3'3'-iminodipropionitrile (IDPN), were measured in rats using an automated photocell device in the context of a routine toxicology study. One hundred Sprague-Dawley rats (10/sex/group) were dosed with vehicle, ACR (10 and 30 mg/kg/day) or IDPN (50 or 125 mg/kg/day), by oral gavage 7 days per week for 5 weeks (except where otherwise indicated). Motor activity was measured in 5-min test sessions prior to initiating treatment, 6 and 24 h after the first dose, and weekly thereafter. Significant mortality occurred in high-dose ACR animals during Week 3. A 10-or 7-day recovery period was initiated after 20 or 22 daily doses for high-dose ACR and IDPN animals, respectively; after which, the high dose ACR and IDPN animals, respectively; after which, the high dose of ACE: was lowered to 20 mg/kg/day. Rapid habituation to the test environment occurred over the 5-imin testing sessions. Significant depressions in activity were observed in high-dose ACR males during Weeks 3 and 5 and in high-dose ACR females during Weeks 2-5. High-dose IDPN females showed no significant changes in activity. However, significant activity depressions were noted in males during weeks 1, 3, and 5. When depressions in activity occurred, they were apparent over the entire test session. The sensitivity of activity measures was sufficient to detect a 15% change in activity levels as compared with controls, with sufficient statistical power to meet regulatory requirements. Inclusion of motor activity assessments complements the additional parameters routinely measured in toxicology studies, augmenting hazard identification.