DOPAMINE TRANSPORTER MESSENGER-RNA IS INCREASED IN THE CNS OF ZUCKER FATTY (FA FA) RATS/

The obese Zucker fa/fa rat is characterized by hyperinsulinemia, obesi ty, and altered monoamine metabolism in the central nervous system (CN S), It has been proposed that the changes in monoamine metabolism may contribute to the metabolic pathophysiology of these animals. Because it has been reported that insulin may regulate the catecholamine reupt ake transporters, which terminate monoaminergic synaptic signaling, in the present study we tested whether messenger ribonucleic acid (mRNA) levels for the noradrenergic (NE) or dopaminergic (DA) transporters w ere altered in obese fa/fa vs. lean Fa/Fa Zucker rats. We found signif icantly elevated DA transporter levels in both the ventral tegmental a rea/substantia nigra pars compacta (VTA/SNc) and zona incerta (ZI) of obese Zucker fa/fa rats (164 +/- 24% of control levels, p = .024; and 316 +/- 61% of control levels, p = .019, respectively), Measurement of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE a nd DA synthesis revealed no effect of the fa gene in either NE or DA n eurons. These findings suggest that increased DA clearance, and perhap s decreased DA signaling, may occur in the obese Zucker fa/fa rat. Pub lished 1998 Elsevier Science Inc.