Effect of varenicline on behavioral deficits in a rat model of Parkinson’s disease induced by unilateral 6-hydroxydopamine lesion of substantia nigra

Abstract

Nicotinic acetylcholine receptors (nAChRs) are implicated in the pathogenesis of Parkinson's disease (PD). Varenicline tartrate is a partial agonist at α4β2 and full agonist at α7 neuronal nAChR subunits. A unilateral lesion of the substantia nigra (SN) has been used as a reliable model of PD. This study aimed to investigate the effect of varenicline on locomotor and nonlocomotor behavioral deficits induced by a unilateral lesion of the SN induced by 6-hydroxydopamine (6-OHDA) (8 µg/4 µl). Varenicline (1 mg/kg) was administered to the lesioned rats daily for 2 weeks, which commenced 3 weeks after 6-OHDA administration. The results showed that varenicline improved motor deficits induced by 6-OHDA. It improved locomotor and nonlocomotor activities such as forelimb use, rotarod performance, and forelimb asymmetry. Varenicline did not change rearing or vibrissae-elicited forelimb placing but did increase apomorphine-induced rotation. In conclusion, the present results suggest that drugs with specific partial/full agonistic activity on nAChR subunits could be of value in the treatment of neurodegenerative disorders such as PD.

Therapeutic Potential of Low-Intensity Magnetic Field Stimulation in 6-Hydroxydopamine Rat Model of Parkinson’s Disease: From Inflammation to Motor Function

“…22,23 A significant reduction in the latency of fall was observed at all speeds in fixed speed protocol as well as in the accelerating speed protocol following 6-OHDA administration, suggesting postural instability. 24,13 We also observed a reduction in stride length, an increase in the base of support, and a decrease of overlap between the forelimb and hind limb, which indicated the rats walking with short strides and wider stance for weight bearing. The behavioral data indicate an overall deficiency in motor functions of the PD rats which was consistent for the complete study period.…”

Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease

“…In accordance, Sharma et al ( 8 ) demonstrated that haloperidol-induced Parkinsonism is attenuated by varenicline in mice. In the same direction, varenicline improved motor deficits induced by 6-OHDA administration in rats ( 7 ). Additionally, administration of varenicline is associated with the reduction of dyskinesias induced by L-DOPA treatment in a PD model in rodents ( 19 ).…”

“…Despite that, to date, only a few studies addressed the possibility that varenicline, similarly to nicotine, protects the dopaminergic system in PD. Varenicline prevents substantia nigra neurodegeneration induced by 6-hydroxydopamine as well as haloperidol-induced parkinsonism ( 7 , 8 ). As dopaminergic degeneration evoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure is widely used as a PD model in rodents, as well as a means to investigate the neuroprotective potential of compounds that modulate MPTP-induced effects, here, we investigated whether chronic varenicline has protective effects on behavior and the dopaminergic system in a MPTP mice model.…”