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Validation of an auditory startle response system using chemicals or parametric modulation as positive controls
Brian R Marable1, Jacques P J Maurissen
1Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA. BRMarable@dow.com
Neurotoxicology and Teratology
|March 17, 2004
Summary
Chemicals may not always be required for validating automated test systems. Parametric modulation, like varying sound intensity, can effectively validate auditory startle response (ASR) systems, offering an alternative to chemical validation.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Regulatory guidelines often require chemical validation for automated neurotoxicity test systems.
- Alternative methods for test system validation are being explored to reduce reliance on chemicals.
Purpose of the Study:
- To investigate whether parametric modulation can serve as an alternative to chemical validation for an automated auditory startle response (ASR) system.
- To assess the effects of specific drugs and varying sound intensities on ASR in Sprague-Dawley rats.
Main Methods:
- Experiment 1: Adult and weanling rats were administered d-amphetamine or clonidine to measure effects on ASR peak amplitude (ASR PA).
- Experiment 2: Rats were exposed to auditory stimuli of varying intensities and null trials to detect intensity- and sex-dependent differences in ASR PA.
- ASR was recorded over multiple trials to assess habituation and response amplitude.
Main Results:
- In adult rats, clonidine decreased ASR PA, while d-amphetamine increased it. In weanlings, clonidine had similar effects, but d-amphetamine's effects were not significant.
- Neither drug significantly affected ASR habituation.
- Experiment 2 revealed statistically significant sex- and intensity-dependent differences in ASR PA.
Conclusions:
- Parametric modulation, demonstrated by varying sound intensity, can effectively validate automated ASR systems.
- These findings suggest that non-chemical methods, such as parametric modulation, can be a viable alternative for validating automated test systems in certain contexts.