[Behavioral and neurochemical methods in research on new psychotropics]

Since the discovery of the antipsychotic effects of chlorpromazine by the French psychiatrists DELAY and DENIKER in 1952, preclinical pharmacologists have proposed several laboratory tests, that have been used to demonstrate the potential activity of drugs in the treatment of mental disorders including schizophrenia, depressive illness and anxiety. Tests are divided into behavioural tests and neurochemical tests. Electrophysiology tests are not considered in this paper. Concerning schizophrenia, although there is no valid model, behavioural tests presently used are: antagonism against various responses induced by dopamine receptor agonists, inhibition of conditioned behaviours, latent inhibition, startle reaction, models related to the neurodevelopmental hypothesis. For antidepressant activity, models are based on antagonism of various effects of reserpine. More anthropomorphic models involve helplessness behaviours, social isolation, changes induced by limbic system lesions. Biochemical investigations mainly involve in vitro and in vivo tests: study of changes in the metabolism of neurotransmitters using microdialysis and other procedures, interaction with receptor subtypes. As a result of advances in molecular biology, other tools are now emerging, but classical tests remain useful.