Elucidation of the neurobiology of depression: insights from a novel genetic animal model

Development of drugs for the effective treatment of depressive disorders re quires elucidation of factors that are critical for clinically antidepressa nt effects. During the past 4 years, we have studied in situ neurochemical alterations in the brain that may underlie depressive behavior. This was ac hieved using the genetically-selected Flinders Sensitive Line (FSL) of rats (a unique animal model of depression), before and after chronic antidepres sant treatment. This line of rats exhibits behavioral features characterist ic of depression, and responds to chronic, but not acute, antidepressant tr eatments. This review summarizes our findings concerning the local neuro-dy namics in the brain during manifestation of depressive behavior and effecti ve antidepressant treatment in this animal model of depression. Understandi ng the abnormalities manifested in neurochemical pathways during depressive disorders and the dynamic effects of these abnormalities on the onset of a ction and efficacy of pharmacological treatments are crucial for the develo pment of effective antidepresssant drugs and therapeutic strategies. (C) 20 00 Elsevier Science Ltd. All rights reserved.