[The importance of in vivo pharmacology in fundamental research on psychotropic drugs and their biological targets].

The main families of psychotropic drugs have been almost fortuitously discovered, from investigations carried out directly in humans. The burst of studies triggered by these discoveries and the considerably strengthened ethical guidelines for clinical trials have allowed remarkable developments in preclinical studies performed in animals, and especially in rodents. The corresponding models may be classified as follows: homologous models mimicking the aetiology of the disease against which one attempts to develop drugs; isomorphic models mimicking specific symptoms of a disease but involving different aetiological mechanisms; predictive models, which assess the effect of a drug on behavioural or other functional signs/symptoms unconnected to the psychiatric disease but involving the same type of biological targets as those affected by the disease; and theoretical or explanatory models that aim to elucidate the mechanism of action of agents producing psychotropic effects. Among the latter, the following can be cited: the knock out of genes coding for a specific biological target; the neutralisation of a specific ARNm by antisense oligodeoxynucleotides, which also aims to prevent the synthesis of a specific biological target; use of controlled reproduction to achieve a concentration of genes, the association of which leads to the development of a disease. Each one of these approaches has been illustrated by an example developed within the Rouen Neuropsychopharmacology Unit: the psychobehavioural spectrum of mice with invalidation of the gene coding for adenosine A2A receptors; the abolition of either nociceptin ORL1 receptors or neurotensin NTR2 receptors in order to characterise their functions; the concentration, by controlled breeding in mice, of a phenotype corresponding to that of depression. These developments illustrate several recent developments in neuropsychopharmacology with the aim of emphasising the vitality of this discipline.