Animal Models and Ethological Strategies for Early Drug-Testing in Humans

Abstract

The preclinical evaluation of psychotropic drugs relies on the use of animal tests which are thought to generate clinically relevant information concerning the psychiatric condition for which the drug can be used. Despite their importance, views on the usefulness of animal “models” vary widely, ranging from outright negation on the grounds that human minds are unique, to the more biological view that because of a partially common phylogenetic history, animals share many behavioural features with humans, e.g. learning, attention, aggression or sociality, which are altered in psychiatric disorders. The widespread use of ethology with its emphasis upon the function and origin of behaviour, particularly social behaviour, is based upon this evolutionary view. Many ethopharmacological tests in animals use situations which bias the animal's behaviour towards flight or sociality but their validation requires clinical feedback from humans. Unfortunately, information relating to human social mechanisms is rarely obtainable from conventional clinical-assessment schemes. To help overcome this problem, we have applied ethological principles to a new Challenge Interview Situation which is designed to bias the behaviour of healthy subjects towards flight. Analysis shows that by staring, moving closer or asking the subjects to relate emotional experiences, shifts in non-verbal behaviour towards avoidance and mild social withdrawal are achieved which resemble behavioural strategies recorded ethologically in depressed patients as well as animals in an arrested flight situation. The Challenge Interview is intended for early drug studies in humans where sociality is a target and can be adapted for concomitant endocrine and biochemical studies if required.