Shati/Nat8l (Shati) is a novel N-acetyltransferase identified in the brain of mice treated with methamphetamine (METH). Recent studies showed that Shati overexpression in the nucleus accumbens (NAc) attenuates pharmacological response of methamphetamine (METH) via mGluR3. Meanwhile, it is reported that after METH self-administration and during reinstatement, dopamine (DA) and glutamate dysregulations were observed in medial PFC (mPFC) and NAc of rats. However, the regulatory mechanism of control over-reward system and the function of Shati in mPFC have not been clarified.
In this study, we injected AAV-Shati vector into the mPFC of mice. Interestingly, Shati injected mice attenuated METH-induced conditioned place preference (CPP) but not locomotor activity. Additionally, immunohistochemistry of mice injected with GFP in mPFC showed an mPFC-NAc top-down regulation. Finally, in vivo microdialysis experiments showed a decrease in DA baseline and METH-induced increased DA in the NAc. Moreover, a decrease in extracellular glutamate levels was also observed in the NAc.
These results suggest that Shati overexpression in mPFC attenuates METH-induced CPP by decreasing extracellular DA in the NAc.