Animal models for controlling and quantifying voluntary muscle performance of rats using operant conditioning

摘要

Two in vivo animal models for controlling and quantifying voluntary exertions of the rat upper and lower limbs are described. Using intact rats, operant conditioning with food rewards is used to produce repetitive and uniform patterns of volitional responding that can be maintained in daily sessions conducted up to several weeks duration. In the upper limb model rats are operantly conditioned to press on a force lever that records response force in real time. Response force and the pattern of responding can be controlled by programming force and other response criteria in the contingencies that determine when and how often responses are reinforced. In the hind limb model, rats are operantly conditioned to perform a voluntary lifting task to generate controlled movement of the plantar flexors. The apparatus allows the rat to enter a tube through an opening in the test chamber, insert its neck into a donut-shaped ring assembly, and lift the assembly. A load cell embedded in a platform at the bottom of the tube measures the dynamic force exerted by the plantar flexors. Weights can be placed on pans attached to the ring assembly to vary the load. The range of motion, velocity, and acceleration of the lift can be determined. Both upper- and lower-limb models are computer automated. There are several advantages of these models compared to invasive in vitro or in situ preparations of isolated muscle fibers or other in vivo models such as rodent dynamometry and treadmill running. Biomechanical parameters such as the force, duration, and rate of responding can be precisely controlled by manipulations of the reinforcement contingencies, while leaving the muscle-tendon complex and normal neuromuscular control processes intact. Also, limitations associated with anaesthesia or forced running that are common in other models are eliminated or minimized. When combined with biomechanical, biochemical, and histological analyses, these models can provide comprehensive methods for studying muscle pathomechanics and work-rest cycles that will broaden the scope of musculoskeletal research.