Altered gene expression for catecholamine biosynthetic enzymes and stress response in rat genetic model of depression

Although stress is a major contributory factor in the development of depres sion, the relationship between stress and depression is still unclear. In t his study, we evaluated basal mRNA levels of several genes involved in neur otransmitter biosynthesis and the effect of stress in Flinder's Sensitive L ine (FSL), a genetic rat model of depression. In adrenals, basal levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolam ine N-methyltransferase (PNMT) and GTP cyclohydrolase I (GTPCH) mRNAs were markedly elevated in FSL rats compared to the control strain. As opposed to control strain, immobilization stress (IMO) to FSL rats, did not further r aise DBH, PNMT or GTPCH mRNAs and had relatively mild effect on TH. In cont rast to enzymes involved in catecholamine biosynthesis, basal NPY and its r esponse to IMO were unchanged in FSL rats. In the brain, the two major dopa minergic nuclei displayed differences. In substantia nigra, TH mRNA levels were similar in both strains, and elevated by IMO only in FSL rats. In vent ral tegmental area in FSL rats, TH mRNA was 2-fold higher than in the contr ol strain and not further elevated by NO. These high basal mRNA levels and abnormal response to stress in several catecholaminergic cell types in FSL rats may be related to the manifestations of depression. (C) 1998 Elsevier Science B.V. All rights reserved.