Introduction: Clinically, metformin has been used as a cornerstone medicine in blood sugar homeostasis for further than 40 times It was obviously the first line treatment among type 2 diabetes mellitus (T2DM) cases.
Recently, fresh places of metformin in cancer & neurodegenerative conditions came apparent. Then, we delved the capabilities of this magic medicine in enhancing motor performance, dopamine (DA) release and TH- protein expression.

Methods: C57BL/6 mice were grouped into 4 via; Group1 (Saline), Group2 (MPTP), Group3 (MPTP + Met200), Group4 (MPTP + Met400). After acute administration of MPTP (25mg/ kg for 5- successive days) and attendant
follow-up by metformin (200 & 400 mg/ kg), mice were exposed to several behavioral tests and later sacrificed for amperometric DA release measures.
Results: MPTP mice showed a significant drop in motor functions and amperometric amplitude (P<0.05) as well as the vesicle recycling as measured by pair-pulse ratio. Interestingly, metformin proves decisive in mollifying the motor dysfunctions caused by MPTP, with Met400 being more potent. It inversely improves the DA release as well the expression of its biomarker (Tyrosine Hydroxylase) in both striatum and Substantia Nigra pars compacta. This in substance, has always indicated a functional part of metformin in employing the motor functions and DA release in the Parkinson’s disease (PD) mode.

Conclusion: Our study demonstrated that metformin enhances motor function, DA release and DA expression in C57BL/6 exposed to acute MPTP-induced neurotoxicity possibly through vesicle recycling. These findings may
facilitate the clinical application of metformin in the treatment of motor and even non-motor symptoms of PD.

KEYWORDS: Metformin; Parkinson’s Disease; Dopamine Release; MPTP; Motor Performance

Received on, 28 February 2025

Accepted on, 06 May 2025

Published on, 12 May 2025