Animal tests, memory function

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

Many of the same issues raised with respect to experimental animal studies also apply to human testing and to the choices of particular tests to be utilized. There are numerous tests that can be utilized for measurement of behavioral functions in humans, and questions remain as to the correct choice. One consideration related to the various tests is deemed validity and refers to the degree to which the test actually measures the behavioral function that it was designed to measure. For example, does a test of memory really evaluate memory function In addition, how specifically does the test measure that function The related issue was raised in experimental animal studies in which the possibility that changes in motor, sensory, motivational processes, etc. might contaminate a measure of memory function, and appropriate controls were included in the more advanced procedures to evaluate those possibilities. 

The primary approach currently used to detect and characterize potential neurotoxicants involves the use of animal models, particularly rodents. Behavioral and neurophysiological tests, often similar to the ones used in humans, are typically administered. The sensitivity of these measures to neurotoxicant exposure is widely accepted. Although it is often not possible to test toxicant effects on some higher behavioral functions in animals (e.g., verbal ability, cognitive flexibility), there are other neurobehavioral outcomes such as memory loss, motivational defects, somatosensory deficits, and motor dysfunction that can be successfully modeled in rodents. These behaviors are based on the ability of the nervous system to integrate multiple inputs and outputs, thus they cannot be modeled adequately in vitro. Although the bulk of neurotoxicity data has been collected in rodents, birds and primates are also used to model human behavioral outcomes. 

More in-depth behavioral tests are required if dose-related toxicant effects are noted in screening tests. These tests may also be required as part of more selective toxicological screening, such as for developmental neurotoxicity. Focused tests of neuromotor function and activity, sensory functions, memory, attention, and motivation help to identify sites of toxicant-mediated lesioning, aid in the classification of neurotoxicants, and may suggest mechanisms of action. Some of these tests, like the schedule-controlled operant behavior tests for cognitive function, require animal training and extensive operator interaction with the animals. 

This test exploits a natural tendency of rodents to explore novel objects and to show an exploratory preference for replaced or displaced objects. The dependence of object recognition memory on the hippocampus is related to the protocol of a test. Short delays between initial exploration phase and a memory test make ORtest independent from the hippocampus (136), however, when longer delays (hours) are implemented, OR memory depends on hippocampus function (158, 159). Object memory impairment is demonstrated when an animal shows no preference in exploration (close proximity, nose contact) of a new or displaced object. 

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