FOOD-DEPRIVATION DECREASES MESSENGER-RNA AND ACTIVITY OF THE RAT DOPAMINE TRANSPORTER

We have hypothesized that the midbrain dopamine (DA) neurons are a tar get for insulin action in the central nervous system (CNS). In support of this hypothesis, we have previously demon strated that direct intr acerebroventricular infusion of insulin results in an increase in mRNA levels for the DA reuptake transporter (DAT). In this study, 24- to 3 6-hour food deprivation was used as a model of decreased CNS insulin l evels, to test whether DAT mRNA levels, DAT protein concentration or D AT functional activity would be decreased. DAT mRNA levels, assessed b y in situ hybridization, were significantly decreased in the ventral t egmental area/substantia nigra pars compacta (VTA/SNc) (77 +/- 7% of c ontrols, p < 0.05) of food-deprived (hypoinsulinemic) rats. Binding of a specific high-affinity DAT ligand (I-125-RTI-121) to membranes from brain regions of fasted or free-feeding rats provided an estimate of DAT protein, which was unchanged in both of the major terminal project ion fields, the striatum and nucleus accumbens (NAc). In addition, we utilized the rotating disk electrode voltametry technique to assess po ssible changes in the function of the DAT in fasting (hypoinsulinemic) rats. The V-max of DA uptake was significantly decreased (87 +/- 7% o f control, p < 0.05), without a change in the K-m of uptake, in striat um from fasted rats. In vitro incubation with a physiological concentr ation (1 nM) of insulin resulted in an increase of striatal DA uptake to control levels. We conclude that striatal DAT function can be modul ated by fasting and nutritional status, with a contribution transporte r by insulin.