- Abstract Development of drugs for the effective treatment of depressive disorders requires elucidation of factors that are critical for clinically antidepressant effects. During the past 4 years, we have studied in situ neurochemical alterations in the brain that may underlie depressive behavior. This was achieved using the genetically-selected Flinders Sensitive Line (FSL) of rats (a unique animal model of depression), before and after chronic antidepressant treatment. This line of rats exhibits behavioral features characteristic of depression, and responds to chronic, but not acute, antidepressant treatments. This review summarizes our findings concerning the local neuro-dynamics in the brain during manifestation of depressive behavior and effective antidepressant treatment in this animal model of depression. Understanding the abnormalities manifested in neurochemical pathways during depressive disorders and the dynamic effects of these abnormalities on the onset of action and efficacy of pharmacological treatments are crucial for the development of effective antidepresssant drugs and therapeutic strategies.