Abstract
A physically active lifestyle is associated with better health in body and mind, and it is urgent that supporting agents for such lifestyles be developed. In rodents, voluntary locomotor activity as an active physical behavior may be mediated by dopaminergic neurons (DNs). Thiamine phosphate esters can stimulate DNs, and we thus hypothesized that thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative, promotes locomotor activity via DNs in rats. Acute i.p. administration of TTFD enhanced rat locomotor activity in a normal cage. In vivo microdialysis revealed that TTFD-enhanced locomotor activity was synchronized with dopamine release in the medial prefrontal cortex (mPFC). Antagonism of the dopamine D1 receptor, but not D2 receptor, in the mPFC fully suppressed TTFD-enhanced locomotor activity. Finally, we found a TTFD dose-dependent increase in voluntary wheel running. Our findings demonstrate that DNs in the mPFC mediates TTFD-enhanced locomotor activity, suggesting the potential of TTFD to induce active physical behavior.
Highlights
The higher the level of physical activity, the higher the levels of physical fitness
tetrahydrofurfuryl disulfide (TTFD) increased the total voluntary activity for the entire 90 min (P < 0.01, Fig. 1A), and we found a biphasic enhancement of TTFD-induced voluntary activity at 10 to 20 min and 50 to 90 min after administration (P < 0.01, Fig. 1B)
Serotonin levels remained basically unchanged but increased at 70 min after administration (P < 0.05, Fig. 2E). These results indicate the possibility that TTFD-enhanced voluntary activity is due to dopaminergic activation in the medial prefrontal cortex (mPFC)
Summary
The higher the level of physical activity, the higher the levels of physical fitness. Amphetamine (AMPH) injection induces dose-dependent dopamine release in the mPFC and increases voluntary locomotor activity through the dopamine D1 receptor in rats[16,17,18]. These data suggest that DNs in the mPFC are a potential target of agents that induce motivation for physical activity. We must be careful of addiction induced by drugs such as AMPH19, thiamine tetrahydrofurfuryl disulfide (TTFD), a popular thiamine derivative, is a potential agent for the activation of DNs without severe side effects. The local injection of TTP and TDP into the rat striatum increases dopamine release[25], suggesting a possible role of TTFD on DNs in the brain. We hypothesized that TTFD has important effects on the brain and contributes to the induction of physical activity via D1-receptor-mediated dopaminergic activity in the mPFC
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