Blockade of fast A-type and TEA-sensitive potassium channels provide an antiparkinsonian effect in a 6-OHDA animal model.

ABSTRACT

OBJECTIVE: To evaluate the effect of K+ channels inhibitors in treatment of parkinson`s disease (PD). METHODS: This prospective comparative study was conducted in the Qazvin University of Medical Sciences, Iran, from April 2015 to January 2016. Male rats (n=37) received intraperitoneal doses of TEA (2 and 5 mg/kg) or 4-AP (0.5 and 1 mg/kg) twice-daily, before a stereotactic injection of 6-hydroxydopamine (6-OHDA) for the following 7 days. The 6-OHDA was injected into right medial forebrain bundle (MFB) of the rat brains. Development and severity of PD were assessed using the apomorphine-induced rotational test, the elevated body swing test and rotarod tests. Concentration of malondialdehyde (MDA), a marker of oxidative stress, was measured in rat sera. RESULTS: Tetraethylammonium and 4-AP significantly reduced the number of apomorphine-induced rotations and improved motor learning in the rotarod test at both doses. Administration of 4-AP and TEA together was more effective than single administration of either agent. Malondialdehyde measurement showed that pretreatment with TEA could not prevent 6-OHDA-induced oxidative stress. CONCLUSION: Our results showed that pretreatment with TEA and 4-AP has a neuroprotective effect against 6-OHDA in dopaminergic neurons in the substantia nigra.