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.