The beneficial effects of drugs that act via
nicotinic acetylcholine receptors (nAChRs) on
Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition.
Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated
varenicline effects in a
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to
varenicline (2 mg/kg) by gavage. After that,
MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate
dopamine and
DOPAC levels. To verify whether
varenicline was protective during the
MPTP insult, a separate group of
MPTP animals received
varenicline from PN90 to PN124.
MPTP reduced cortical
dopamine content and increased
dopamine turnover. Those effects were not reversed by
varenicline treatment. Interestingly,
varenicline reversed the
MPTP-induced hyperactivity in the open field. Both maintenance of
varenicline treatment during
MPTP exposure or its interruption before
MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that
varenicline treatment reduced the
MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect,
varenicline could exert
neuroprotective effects on circuits that control motor activity in PD.