The overall goal of this proposal is the development of the force-plate actometer as an instrument to provide quantitative measurements of rodent behavior, including locomotor activity, tremor, rotational activity and amphetamine-induced focused stereotypies. Unlike video tracking systems, the sampling rate can be varied to accommodate experiments requiring rates above 30 frames/s, and the programmable sampling rate facilitates synchrony between behavioral and electronically recorded physiological data. This versatile instrument, which can replace several different instruments, will find application in pharmacology, toxicology, behavioral genetics and behavioral neuroscience. The force-plate actometer will make possible quantitatively reliable measures of rodent behavior across laboratories and the has the potential to accelerate preclinical biomedical discovery related to a wide range of central nervous system disorders by providing relatively high throughput, multidimensional screening for gene manipulations in mice or rats. The ability of the device to quantitate the behavioral effects and neurotoxicity of drug candidates coupled with GLP grade software offers numerous applications in preclinical drug testing. Initially, two new prototype devices, one optimized for rats, the other for mice, will be constructed, tested and validated. Simultaneously, a detailed software development plan will be prepared for the program that will integrate data collection, storage and analysis. The final package, to be written in Phase II, will be validated, commercial grade software written in accordance with FDA mandates for Investigational New Drug applications. Among the parameters to be tested are force plate stiffness and weight (mass), effects of isolation from environmental vibration and sound, and sampling rate. The conditions for testing sampling rates will be amphetamine-induced stereotypy in rats given 5.0 mg/kg of amphetamine and tremor in C57BL/6 mice induced by harmaline. In Phase I, validation will be carried out by comparing the force-plate actometer results with those obtained for the same sessions by a computer-based video tracking system. Again the test conditions will be motor-activating doses (1.0 mg/kg) and focused stereotypy inducing doses (5 mg/kg) of amphetamine or saline in rats. Although C57BL/6 mice do not show a rat-like response, the 5 mg/kg dose will be tested for activating effects in the mice. During Phase II, the scores from force-plate-measured stereotypies will be compared to simultaneously collected and manually scored, flame-by-frame video tape recordings. Also during Phase II, the feasibility of making chemical measurements such as neurotransmitter concentrations, monitored via brain microdialysis sampling, simultaneously with the collection of behavioral data will be investigated in rats exhibiting amphetamine-induced focused stereotypies during 3-hr sessions.
