The Functional Observational Battery (FOB) has long been used with rodents as an initial screening device to assess the neurotoxic potential of candidate drugs and environmental toxins. However, large animals may be more appropriate models for certain drug classes. Battelle has modified the standard rodent FOB protocol for use with large animal models in cases where rodents do not provide suitable data. The modified FOBs were designed for use in large animal models.
The rodent version of the FOB has been used for decades for neurobehavioral testing and rapid neurotoxicity screening for candidate drugs. The standard battery consists of 40+ tests to assess central nervous system (CNS) and peripheral nervous system (PNS) effects including excitability, neuromuscular coordination, general activity, posture, grip strength, presence of tremors or convulsions, autonomic nervous system function, spontaneous activity, motor activity, arousal, sensory/motor reflex responses and body temperature. The battery includes observations under home cage, open field and handling conditions.
Modifying the FOB for use in large animals requires a deep understanding of the variations in the physiology, behavior and psychology of each species. For example, grip tests appropriate for rats cannot be directly translated to large animals whose extremities are not made for gripping. Similarly, standards for normal and stressed behavior under open field conditions for rats,a prey species, are very different from those in larger animals of a predator species. In some cases, standard rodent tests are simply not practical or feasible for larger species; “open field” conditions for NHPs are difficult to create in a lab environment.
Battelle researchers analyzed the 40+ tests in the standard rodent FOB and developed a set of modified tests, procedures and evaluation standards appropriate for two large species. They then characterized and developed a series of home cage and open field tests for rapid CNS screening in rats and the two large animal species. All three were tested using the FOB under a sedative and a stimulant. Researchers were able to then compare the behavioral and CNS effects on the different species at different dosages. The study showed that FOB data in both species can discriminate between the behavioral effects of stimulant and sedative drug treatments. Furthermore, these findings are consistent with behavioral effects demonstrated in the rodent model.
The FOB studies were part of internal research conducted at Battelle in order to expand the services we are able to offer our clients. As a nonprofit, mission-driven research organization, Battelle continually reinvests in internal research studies to advance our understanding of critical problems faced by the research community.
Battelle is also working to develop new methods to collect neurobehavioral and cardiovascular data simultaneously. By expanding the scope of data collected during a single study, we can achieve the very important goal of reducing the overall number of animals used for safety pharmacology and environmental toxicology studies. Researchers will share results from recent validation studies in an upcoming issue of Battelle CRO+ Today and at the fall conferences for the Safety Pharmacology Society and the Society for Neuroscience.