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

Neurosciences (Riyadh). 2017 Jan;22(1):44-50. doi: 10.17712/nsj.2017.1.20160266.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology*
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Apomorphine / antagonists & inhibitors
  • Apomorphine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Malondialdehyde / blood
  • Medial Forebrain Bundle / drug effects
  • Neuroprotective Agents / pharmacology
  • Oxidopamine*
  • Parkinson Disease, Secondary / blood
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / prevention & control*
  • Potassium Channel Blockers / pharmacology*
  • Rats
  • Rotarod Performance Test
  • Tetraethylammonium / pharmacology*

Substances

  • Antiparkinson Agents
  • Neuroprotective Agents
  • Potassium Channel Blockers
  • Malondialdehyde
  • Tetraethylammonium
  • Oxidopamine
  • 4-Aminopyridine
  • Apomorphine