Dexmedetomidine attenuates the induction and reverses the progress of 6-hydroxydopamine- induced parkinsonism; involvement of KATP channels, alpha 2 adrenoceptors and anti-inflammatory mechanisms.

Abstract

BACKGROUND:

Studies have shown that dexmedetomidine (DEX), a potent α2-adrenoceptors agonist provides neuroprotection through suppression of inflammatory response. In present study, we examined effect of DEX and its underlying mechanisms on the induction and progress of 6-OHDA- induced Parkinsonism in rat.

MATERIAL AND METHODS:

The 6-OHDA was injected into the medial forebrain bundle of right hemisphere by stereotaxic surgery and then, behavioral tests carried out within second, fourth, sixth and eighth weeks post-surgery. All treatments were started before the toxin and continued to eight weeks afterwards. Striatal levels of dopamine, TNF-α and IL-6 were measured within the eighth week after the toxin by enzyme-linked immunosorbent assay kits.

RESULTS:

DEX at dose of 50 μg/kg attenuated significantly the intensity of 6-OHDA- induced behavioral symptoms in the second week post-surgery. DEX also attenuated remarkably 6-OHDA- induced reduction in striatal dopamine level. These effects were also observed in rats treated by both DEX and yohimbine (YOH), a selective α2-adrenoceptors antagonist but were not observed in rats treated by both of DEX and glibenclamide (Glib), an ATP-sensitive potassium (KATP) channels blocker. DEX also reversed the progressive increase in intensity of the behavioral symptoms and reversed 6-OHDA- induced overproduction of TNF-α and IL-6. These effects were reversed by YOH but not Glib.

CONCLUSION:

Our findings indicate that DEX attenuates the induction and reverses the progress of 6-OHDA- induced Parkinsonism through activation of KATP channels and α2-adrenoceptors, respectively. Through activation of α2-adrenoceptors, DEX also exerts anti-inflammatory effect which is possibly another mechanism underlying the DEX's antiparkinsonism effect.

• Authors: Azita Minaei, Hashem Haghdoost-Yazdi
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 382 Pg. 114743 (11 01 2019) ISSN: 1096-0333 [Electronic] United States
• PMID: 31476326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Anti-Inflammatory Agents
• Inflammation Mediators
• KATP Channels
• Receptors, Adrenergic, alpha-2
• Dexmedetomidine
• Oxidopamine

Topics

• Adrenergic alpha-2 Receptor Agonists (pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Dexmedetomidine (pharmacology, therapeutic use)
• Disease Progression
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• KATP Channels (agonists, metabolism)
• Male
• Oxidopamine (toxicity)
• Parkinsonian Disorders (chemically induced, metabolism, prevention & control)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, alpha-2 (metabolism)