Tyrosine hydroxylase mRNA levels in locus coeruleus of rats during adaptation to long-term immobilization stress exposure

The major central norepinephrinergic nucleus, locus ceruleus (LC), is thought to participate in modulation of such brain areas as cerebral cortex, septum, hippocampus, thalamus, hypothalamus, and cerebellum in animals facing various physiological challenges, including stress. Exposure of experimental animals to different stressors causes an increase in LC activity and gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. The aim of this work was to investigate the effect of a single and repeated (7 times) or long-term repeated (42 times) daily immobilization stress (IMMO) on TH mRNA levels in LC of laboratory rats by in situ hybridization method. A single IMMO caused significant elevation of LC TH mRNA levels in comparison to unstressed controls. This was found immediately and at 3 and 6 h after IMMO, and progressively increased up to 24 h after the first IMMO terminated. Further exposure to IMMO did not cause additional increases in LC TH mRNA levels, which stayed significantly elevated in comparison to unstressed rats. In animals that underwent IMMO for 42 times, the LC TH gene expression, 24 h after the last stress exposure, was significantly lower when compared to that of singly or seven times stressed rats. Thus, our results indicate a possible adaptation of catecholamine-synthesizing system at the level of TH gene expression in LC of rats exposed to long-term repeated IMMO.