Novel action of metformin in the prevention of haloperidol-induced catalepsy in mice: Potential in the treatment of Parkinson's disease?

Metformin is widely used to treat type II diabetes and other metabolic syndromes. In addition, it has been shown to increase neurogenesis, spatial memory formation and reduce the risk of Parkinson's disease. On this basis, the aim of the present study was the investigation of the protective potential of metformin in the haloperidol-induced catalepsy model of Parkinson's disease in mice. The effect of metformin (20 - 100mg/kg, p.o) on motor coordination was assessed using rotarod and forced swimming tests (FST), while the effect on memory function was evaluated using the Y-maze test. The neuroprotective activity was investigated in acute/chronic (21days) haloperidol-induced catalepsy in mice. On the 21st day, biochemical estimation of nitrosative and oxidative stress parameters was carried out. Metformin (50 or 100mg/kg, p.o.) did not affect motor coordination in rotarod test and FST but significantly reversed haloperidol-induced memory deficit (+35.50%) at 100mg/kg. Importantly, metformin significantly reduced the duration of catalepsy score during acute and chronic catalepsy tests as compared to trihexylphenidyl (reference standard). Intraperitoneal chronic injection of haloperidol (1mg/kg) significantly increased malondialdehyde and nitrite levels, while it significantly attenuated the activity of reduced glutathione, catalase and superoxide dismutase. Moreover, oral chronic administration of metformin significantly attenuated the haloperidol-induced increase of malondialdehyde and nitrite, as well as the deficit of glutathione and catalase. These findings suggest that metformin protects against haloperidol-induced catalepsy through inhibition of oxidative/nitrosative stress and has the potential for adjuvant action in the management of Parkinson's disease.