Compounds such as BPA that increase DAT numbers at the membrane have been reported to be pathological because increased DATs in the membrane leads to increased toxin susceptibility (McArthur et al. 2007).
Lastly, we asked whether increasing DAT levels in DA neurons affected locomotor activity.
In this line, two copies of the HA-DAT BAC are incorporated into the genome, increasing DAT mRNA levels by 47%.
Here we observed that chronic loss of Pmch in the rat resulted in increased presynaptic dopaminergic release capacity, increased DAT levels in the NAc of pmch−/− rats, and an increased trend in NAc gene expression of Syn1 and Vmat2.
We could not confirm the first SPECT studies indicating an increased DAT binding in striatum, but rather obtained results more closely in agreement with the studies indicating an unaltered or decreased binding capacity.
Similarly, in human cocaine addicts, increased, decreased, and no change in DAT levels have been observed, with a preponderance of studies showing increased DAT levels in human addicts.
Thus, determining the role of increased DAT levels in addictive behaviors may allowed for personalized therapies when treating these "at risk" populations.
Whilst individuals with ADHD have been shown to exhibit increased DAT density in the brain [ 18, 19], depressive patients were found to have overall decreased levels of DAT [ 20].
Reduced and increased DAT expression resulted in pronounced decreases and increases in ethanol-induced hyperactivity, respectively, helping to confirm that DA regulates ethanol-induced hyperactivity (Fig. S1A, 2K).
Cocaine increases DA concentrations by blocking the DAT, and chronic drug use results in increased DAT levels and function that are thought to contribute to craving, withdrawal-induced anhedonia and binging.
