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

Abstract

Although stress is a major contributory factor in the development of depression, the relationship between stress and depression is still unclear. In this study, we evaluated basal mRNA levels of several genes involved in neurotransmitter biosynthesis and the effect of stress in Flinder's Sensitive Line (FSL), a genetic rat model of depression. In adrenals, basal levels of tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), phenylethanolamine 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 raise DBH, PNMT or GTPCH mRNAs and had relatively mild effect on TH. In contrast to enzymes involved in catecholamine biosynthesis, basal NPY and its response to IMO were unchanged in FSL rats. In the brain, the two major dopaminergic nuclei displayed differences. In substantia nigra, TH mRNA levels were similar in both strains, and elevated by IMO only in FSL rats. In ventral tegmental area in FSL rats, TH mRNA was 2-fold higher than in the control strain and not further elevated by IMO. 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.