Psychiatric Studies Using Animal Models              Hong CJ, Jul 10, 2006

    Animal model of depression may be used to screen novel antidepressants or as a simulation to investigate the pathophysiology of depressive illness. The essential requirement for an antidepressant screening test is that it can predict antidepressant activity. Ideally, it should also be cheap, reliable and easy to use. We therefore developed the devices of PsyLab auto-FST (USA Patent No. US6,799,535 B2) and PsyLab auto-TST (USA Patent No. US6,955,139 B2) to conduct the forced swimming test (FST) and the tail suspension test (TST), respectively.

    Although the use of animal models by the pharmaceutical industry since the 1970s has resulted in the discovery of an array of antidepressant drugs, the clinical requirement is now to identify rapid onset antidepressant treatments. The success of the FST and TST relying on acute treatment has ironically delayed the development of animal models in which antidepressants are active only following chronic administration. We therefore developed a protocol with minor intermittent stresses to induce chronic learned helplessness of C57BL6J mice. This method may be useful as a screening test and as a model to investigate neuropharmacological mechanisms associated with treatment.

    A DSM-IV diagnosis of major depression requires the presence of at least one of two core symptoms: loss of interest or pleasure and depressed mood. Of these two core symptoms, loss of interest can be modeled in animals, but depressed mood cannot. We modified the method of sucrose preference test and develped an apparatus to evaluate the level of interest of a tested mouse (USA Patent, proved). In the apparatus, a dispenser with 2% sucrose is installed at a higher and tougher position while another dispenser with plain water is relatively easier to access.

    It is widely assumed that individuals vary in their susceptibility to depression, and which is typically precipitated by some genetic diatheses. In order to setup genetic models of depression we are using a battery of hierarchical behavioral tests to screen inheritable depression-like behavior in ENU-mutagenized mice at the Mouse Mutagenesis Program Core Facility (MMP) at the Academia Sinica. Heritability tests are just underway for two pedigrees each with two mice displaying anxious and withdrawn behavior. A pedigree with three mice showing hyperactivity, which is opposite to psychomotor retardation in depression, will be further studied.(slides)

Hong CJ, 2006/7/10