Increased transcription of the tyrosine hydroxylase gene in individual locus coeruleus neurons following footshock stress

Footshock-evoked change in transcriptional activity of tyrosine hydroxylase in neurons of the locus coeruleus was examined using an intron-specific in situ hybridization histochemical technique. A significant increase in the cellular concentration of tyrosine hydroxylase primary transcripts was foun d in locus coeruleus neurons 3 h following 30 min of intermittent footshock . However, the footshock-induced increase in tyrosine hydroxylase transcrip tion was not homogeneously expressed in locus coeruleus neurons. Similarly, administration of the alpha (2)-adrenergic receptor antagonist idazoxan pr oduced a significant increase in the cellular concentration of tyrosine hyd roxylase primary transcripts that was heterogeneously distributed among loc us coeruleus neurons. Both footshock and idazoxan significantly increased t he regional levels of tyrosine hydroxylase messenger RNA in the locus coeru leus. The time-course of changes in tyrosine hydroxylase transcription rate and messenger RNA levels in the locus coeruleus was examined after a 15 mi n exposure to footshock. A robust increase in tyrosine hydroxylase transcri ption rate was found at the end of 15 min of footshock, which remained elev ated for 6 h and was back to the control levels by 24 h. In contrast, in re sponse to a 15 min period of footshock tyrosine hydroxylase messenger RNA c oncentrations in the locus coeruleus did not increase until 6 h and remaine d elevated at 24 h. These findings demonstrate that transcription of the tyrosine hydroxylase g ene in locus coeruleus neurons in response to footshock stress occurs rapid ly, is sustained for many hours and is heterogeneously distributed. These d ata also suggest that the increase in tyrosine hydroxylase messenger RNA fo llowing footshock is mediated, at least in part, by an increase in tyrosine hydroxylase gene transcription. (C) 2000 IBRO. Published by Elsevier Scien ce Ltd. All rights reserved.