Preclinical and clinical behavioral paradigms for testing drugs that affect learning and memory processes
Reddy, D.S.
Methods and Findings in Experimental and Clinical Pharmacology 20(3): 249-277
1998
ISSN/ISBN: 0379-0355 PMID: 9646287 Document Number: 3527
Many experimental models have successfully demonstrated the effect of agents that affect cognition processes in passive avoidance, active avoidance, T-maze, radial maze and water maze tasks. The relationship, however, between such behavioral and biochemical changes is not yet clear. Paradigms with NBM and hippocampal lesions produced by cholinotoxin AF64A, excitotoxins ibotenic, kianic acids and colchicine have shown the involvement of task-specific regions in the learning and memory processes. Although a wide variety of behavioral models for the evaluation of learning and memory processes are currently being used, the interpretation of behavioral parameters in many of these tasks is still ambiguous. For example, without knowing what could have been the cause for a behavioral change, any observed behavioral change has been interpreted in terms of cognitive performance. Task-specific characteristics that could have influenced the performance of the control and experimental group to a different extent, are not generally considered. For example, age-related deficits in spatial discrimination performance have often been interpreted as deficits in spatial information processing. Drug effects should be tested in different types of tasks that tap different aspects of behavior to exclude alternative explanations for the performance in a cognitive task. Consequently, many experimental interpretations are liable to anthropomorphism, as a hasty conclusion about the memory-enhancing effects of a drug should not be stated boldly, but rather in terms of magnitude of modulation of the particular task. The Morris-water maze task is a sensitive model for studying the cognitive processes in rodents that not only reliably reflects the ability of the animal to learn the position of the hidden platform, but also reflects exploratory aspects of behavior. The most widely applied model, the passive-avoidance task paradigm, has given reproducible and dependable results in screening agents that affect learning and memory. Apart from these two tasks, other paradigms such as radial arm maze, Y-maze, elevated plus-maze and drug discrimination tests provide a consistent battery of screening models for the elucidation of the neurobiology of learning and memory and agent that affect cognitive processes. Piracetam, a memory-enhancing drug capable of abolishing the working memory errors, has become a standard drug for comparison. Furthermore, pharmacologically induced impairment of cognitive tasks either with scopolamine or MK-80 1 have become routine tools for the elucidation of specific neurotransmitter and receptor systems in the manipulation of learning and memory processes. A variety of simple and consistent behavioral techniques are also available for the clinical assessment of nootropic and amnestic agents. These rapid development in the field of animal models of learning and memory processes may hopefully lead to an improved understanding of the pathophysiology of Alzheimer's disease, and finally permit the rational designing of novel therapeutic strategies for distinct cognitive dysfunctions.
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