Overexpression of tyrosine hydroxylase in dopaminergic neurons increased sensitivity to methamphetamine

Amphetamine Exposure during Embryogenesis Alters Expression and Function of Tyrosine Hydroxylase and the Vesicular Monoamine Transporter in Adult C. elegans

“…In summary, our data show that continuous exposure to Amph during embryogenesis increases CAT-2/TH and decreases CAT-1/VMAT expression in adult C. elegans via epigenetic mechanisms. Considering that our results are in agreement with data showing that mice overexpressing TH exhibit enhanced Amph-induced behaviors [25,26], and that rats chronically treated with Amph exhibit a long-lasting increase in striatal DA [22], our results establish C. elegans as an efficient and inexpensive model to study the long-lasting physiological modifications caused by prenatal exposure to Amph [37].…”

“…However, when animals were challenged with 0.5 mM Amph for 10 min, we observed significantly increased SWIP in animals exposed to Amph during embryogenesis with respect to animals pre-exposed to control solution (Figure 2c, red and blue circles, respectively). These results confirm our previous reports [12] and resemble recent data showing that mice overexpressing TH exhibited enhanced sensitivity to Amph and elevated striatal DA levels, but no basal hyperdopaminergic behaviors [25,26]. To further investigate the Amph hypersensitivity caused by embryonal exposure to Amph, we quantified cat-2 mRNA in adult animals exposed to Amph during embryogenesis before and after the 10 min of Amph challenge.…”

Decoupling Dopamine Synthesis from Impulsive Action, Risk-related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [18F]-FDOPA PET Study in Roman High- and Low-avoidance Rats

“…Considering that previous studies associated impulsive behaviors with heightened DA release (Bellés et al, 2021) and elevated TH mRNA in the midbrain (Tournier et al, 2013), it is somewhat unexpected that our study found no evidence of altered DA synthesis in impulsive rats. However, a recent study (Nago-Iwashita et al, 2023) showed that TH overexpression does not necessarily result in elevated DA levels, which suggests that additional regulatory mechanisms other than elevated TH expression underly heightened DA release in impulsive subjects. Our findings of preserved DA synthesis in impulsive rats are also consistent with recent neuroimaging studies in humans, where DA synthesis was independent of trait impulsivity (van den Bosch et al, 2023) and RDM (Skandali et al, 2022), despite the relationship between impulsivity and elevated DA release (Buckholtz et al, 2010; Oswald et al, 2015).…”

Decoupling Dopamine Synthesis from Impulsive Action, Risk-Related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [18F]-FDOPA PET Study in Roman High- and Low-Avoidance Rats

“…Considering that previous studies associated impulsive behaviors with heightened DA release ( Bellés et al, 2021 ) and elevated TH mRNA in the midbrain ( Tournier et al, 2013 ), it is somewhat unexpected that our study found no evidence of altered DA synthesis in impulsive rats. However, a recent study ( Nago-Iwashita et al, 2023 ) showed that TH overexpression does not necessarily result in elevated DA levels, which suggests that additional regulatory mechanisms other than elevated TH expression underlie heightened DA release in impulsive subjects. Our findings of preserved DA synthesis in impulsive rats are also consistent with recent neuroimaging studies in humans, where DA synthesis was independent of trait impulsivity ( van den Bosch et al, 2023 ) and RDM ( Skandali et al, 2022 ), despite the relationship between impulsivity and elevated DA release ( Buckholtz et al, 2010 ; Oswald et al, 2015 ).…”