Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats.

Responses of central noradrenergic (NE) neurons to stressors like immobilization (IMO), cold exposure, insulin-induced hypoglycemia, and cellular glucoprivation caused by 2-deoxy-D-glucose (2-DG) were investigated in intact and long-term repeatedly immobilized (LTR, 2 h daily IMO for 41 days) rats. Expression of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT2) genes were determined by using in situ hybridization histochemistry in brainstem A1, A2, A5 and locus coeruleus (LC) neurons. TH mRNA levels were increased by single IMO or 2-DG administration in all areas studied. Cold was effective only in LC and A2 neurons while insulin had no effect. LTR immobilization elevated TH mRNA levels in all investigated cell groups. These elevations were equally high to those elicited by a single IMO in each noradrenergic group, except the LC where LTR IMO was less effective than the single IMO. The levels of NET and VMAT2 mRNAs were elevated only in the A1 and A2 cell groups of LTR IMO rats. A newly applied IMO in LTR rats did not alter TH, NET, and VMAT2 mRNA levels in any NE cell group investigated. Novel stressors like cold and 2-DG exaggerated the increased TH mRNA levels only in the LC of LTR IMO rats, unlike in the other NE cell groups. The present data indicate that repeated exposure of rats to homotypic stressor induces an adaptation of NE neurons, whereas single exposure of such animals to heterotypic novel stressor produces an exaggerated response of the system at the level of TH (in LC) and NET (in A1, A2) gene expression.