Abstract
We have hypothesized that the midbrain dopamine (DA) neurons are a target for insulin action in the central nervous system (CNS). In support of this hypothesis, we have previously demonstrated that direct intracerebroventricular infusion of insulin results in an increase in mRNA levels for the DA reuptake transporter (DAT). In this study, 24- to 36-hour food deprivation was used as a model of decreased CNS insulin levels, to test whether DAT mRNA levels, DAT protein concentration or DAT functional activity would be decreased. DAT mRNA levels, assessed by in situ hybridization, were significantly decreased in the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) (77 ± 7% of controls, p < 0.05) of food-deprived (hypoinsulinemic) rats. Binding of a specific high-affinity DAT ligand (<sup>125</sup>I-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 projection fields, the striatum and nucleus accumbens (NAc). In addition, we utilized the rotating disk electrode voltametry technique to assess possible changes in the function of the DAT in fasting (hypoinsulinemic) rats. The V<sub>max</sub> of DA uptake was significantly decreased (87 ± 7% of control, p < 0.05), without a change in the K<sub>m</sub> of uptake, in striatum from fasted rats. In vitro incubation with a physiological concentration (1 n<i>M</i>) of insulin resulted in an increase of striatal DA uptake to control levels. We conclude that striatal DAT function can be modulated by fasting and nutritional status, with a contribution by insulin.
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Dates
Type | When |
---|---|
Created | 22 years, 4 months ago (April 15, 2003, 3:06 p.m.) |
Deposited | 4 months, 1 week ago (April 24, 2025, 12:25 a.m.) |
Indexed | 6 days, 14 hours ago (Aug. 30, 2025, 12:49 p.m.) |
Issued | 27 years, 8 months ago (Jan. 1, 1998) |
Published | 27 years, 8 months ago (Jan. 1, 1998) |
Published Online | 17 years, 5 months ago (March 19, 2008) |
Published Print | 27 years, 8 months ago (Jan. 1, 1998) |
@article{Patterson_1998, title={Food Deprivation Decreases mRNA and Activity of the Rat Dopamine Transporter}, volume={68}, ISSN={1423-0194}, url={http://dx.doi.org/10.1159/000054345}, DOI={10.1159/000054345}, number={1}, journal={Neuroendocrinology}, publisher={S. Karger AG}, author={Patterson, Terrell Ann and Brot, Michelle D. and Zavosh, Aryana and Schenk, James O. and Szot, Patricia and Figlewicz, Dianne P.}, year={1998}, pages={11–20} }