Haloperidol-induced parkinsonism is attenuated by varenicline in mice

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Abstract
Background: Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). However, there is no known drug to stop/slow down this neurodegeneration. Varenicline is an anti-smoking drug and has the potential to prevent neurodegeneration. Thus, the present study was designed to evaluate the effect of varenicline in animal models of PD. Methods: Levodopa and haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4 were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5 mg/kg, i.p., respectively and group 5 was administered levodopa along with haloperidol. Varenicline was administered daily, 30 min prior to the administration of haloperidol. Varenicline was administered for the first 8 days, and then from the 9th day until the 15th day. Behavioral assessment (rotarod and catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine levels and histopathology were also performed. Results: In the haloperidol-treated groups, significant decrease in latency to fall off (on rotarod) and increase in catalepsy duration (in catalepsy test) were observed as compared to the control group. In the levodopa-treated group, significant increase in latency to fall off the rotarod and significant decrease in catalepsy duration were observed as compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5 mg/kg) significantly increased the latency to fall off the rotarod, while varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency to fall off the rotarod as compared to the haloperidol-treated group. On day 15, significant increase in latency to fall off the rotarod was observed in varenicline (at all doses) as compared to the haloperidol-treated group. In the catalepsy test, the varenicline-treated (at all doses) groups showed significant decrease in duration of catalepsy on day 9 and day 15 as compared to the haloperidol-treated group. Significant decrease in striatal dopamine levels was observed among the haloperidol-treated groups as compared to the control group. Further, varenicline-treated (at all doses) and levodopa-treated groups showed significant increase in striatal dopamine levels when compared with the haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease in neurons. However, the levodopa-treated group did not show any significant decrease in neurons. Thus, varenicline has shown promising results and has provided novel strategy for the treatment of PD.

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