[The approaches in the discovery of antidepressants using affective disorder models].
With the recent appearance of SSRI and SNRI, medication options with respect to depression have broadened. However, patients displaying clear improvement with existing antidepressants still do not exceed about 60 percent of total patients. New types of therapeutic agent development are currently required. Conditions for the determination of new antidepressants are: 1) instantaneous medications displaying a high level of antidepressant action in the early stages of treatment and 2) medications displaying efficacy with respect to patients that are therapy-resistant. However, drug discovery using new animal models is critical as part of drug development of these types of antidepressants in addition to models used in the past such as the forced swim test. We adopted two animal models (olfactory bulbectomy model and conditioned fear stress (CFS) model) developed for pharmacological evaluation of antidepressants. It has been well known that olfactory bulbectomied rats display extreme emotional response (aggressiveness and anxiety). However the improvement of this response occurs following chronic but not acute antidepressant treatment. Thus, we used this model to evaluate the period of the manifestation of antidepressant action. Mice exhibited a marked suppression of motility when they were returned to the same environment in which they had previously received an electric foot shock. Thus, it is suggested that the CFS stress model may be a useful model for therapy-resistant depression due to the fact that motor suppression is not readily attenuated by antidepressant treatment. In this report, we provide an overview of the approaches in the discovery of new antidepressants using these affective disorder models.
Saitoh
Akiyoshi
A
Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41, Ebara, Shinagawa-ku, Tokyo, 142-8501 Japan.
Yamaguchi
Kazumasa
K
Murasawa
Hiroyasu
H
Kamei
Junzo
J
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D008297:Male; D051379:Mice; D019964:Mood Disorders / Q000188:drug therapy* / Q000209:etiology; D009830:Olfactory Bulb / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents