DIABETES CAUSES DIFFERENTIAL CHANGES IN CNS NORADRENERGIC AND DOPAMINERGIC-NEURONS IN THE RAT - A MOLECULAR STUDY

We have previously reported that chronic elevation of insulin in the C NS of rats results in opposing changes of the mRNA expression for the norepinephrine transporter (NET; decreased) and the dopamine transport er (DAT; increased). In the present study we tested the hypothesis tha t a chronic depletion of insulin would result in opposite changes of N ET and DAT mRNA expression, from those observed with chronic elevation of insulin. Rats were treated with streptozotocin to produce hypoinsu linemic diabetes. One week later, steady state levels of mRNA were mea sured by in situ hybridization for NET in the locus coeruleus (LC) and for DAT in the ventral tegmental area/substantia nigra compacta (VTA/ SNc). The mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA synthesis, was measured in these same brain regions. In the diabetic animals, NET mRNA was significantly elevated (159 +/- 22 % of average control level) while DAT mRNA was non-significantly decre ased (78 +/- 9% of average control level). Additionally, TH mRNA was s ignificantly altered in both the LC (131 +/- 11% of average control le vel) and VTA/SNc (79 +/- 5% of average control level). We conclude tha t endogenous insulin is one physiological regulator of the synthesis a nd re-uptake of NE and DA in the CNS.