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Close up of disease.

Battelle Life Sciences Research CRO+ Today

October 2016 - Issue 9

Combined Cardiovascular and Neurobehavioral Testing Streamlines Toxicology Studies

Both cardiovascular (CV) and neurobehavioral testing are needed for Safety Pharmacology evaluations. However, it can be time and cost intensive to conduct a full battery of CV and central nervous system (CNS) tests. One promising solution is to conduct CV and CNS testing simultaneously. A recent Battelle study demonstrates that simultaneous testing produces CV data comparable to data collected during stand-alone CV tests, with the added benefit of also capturing CV changes while animals are actively performing their neurobehavioral tasks.

Simultaneous testing provides significant advantages for safety pharmacology and chemical safety testing. Performing both sets of tests together reduces timelines and costs for companies. It also reduces the number of animals needed to conduct testing, minimizes stress on the animals and allows CV measurement while under baseline conditions, while actively performing in forced or spontaneous activity tests, and under reflex tests.

Using simultaneous testing techniques, researchers can look at changes in telemetric readings and task performance with the same animal under exposed and non-exposed conditions, so that each subject acts as its own control. Taking simultaneous readings also allows researchers to better understand how CV and CNS effects are interrelated. For example, there is a large increase in heart rate seen when animals are performing on the Rotarod that quickly returns to baseline when animals are in their inter-trial interval period. The CV and behavioral profile show similar increases in heart rate and performance with drugs like amphetamine but are discordant with drugs like MK-801, which increases heart rate dramatically but significantly impairs performance.

Battelle researchers are optimizing techniques for simultaneous CV and CNS testing. In part, this involves technical considerations, such as placement of telemetry equipment so that it does not interfere with task performance. Measurement issues, such as the different time intervals for data collection of CV vs. CNS data, also present challenges for simultaneous testing. Battelle researchers have developed data collection and analysis methods to enable close temporal matching of CNS and CV effects.

In the Battelle study, rats instrumented with telemetry transmitters were assessed in a series of CNS tests, including acoustic startle response, motor activity and Rotarod. Measurements for both CV and CNS responses were made under baseline conditions and while subjects were exposed to three drugs with well-understood CV and CNS effects. The results demonstrated accurate simultaneous detection of changes in CV and CNS data during performance of neurobehavioral tasks. Cardiovascular endpoints were impacted by performance in these tasks and by drug challenge.

Battelle researchers are continuing to refine methods for simultaneous CV and CNS testing. These methods will help the pharmaceutical industries streamline studies while providing clear, accurate data needed to understand the CV and neurological effects of their products.