J Biomed Transl Res.  2020 Dec;21(4):165-170. 10.12729/jbtr.2020.21.4.165.

Rotigotine protects dopaminergic neurons through dopamine D2 receptor against 6-hydroxydopamine

Affiliations
  • 1Institute of Animal Medicine & Department of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea
  • 2Laboratory Animal Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea

Abstract

Dopamine (DA) receptor (D1 and D2-like receptors) agonists are known to affect expression levels of DA receptors. Rotigotine, a DA D2-like receptor agonist, has been developed for treating Parkinson’s disease (PD). However, its role in PD by acting through DA D2-like receptors has not been fully understood yet. The purpose of this study was to investigate neuroprotective effects of rotigotine through DA D2 and D3 receptors in 6-hydroxydopamine (6-OHDA) induced mouse model of PD.Expression level of tyrosine hydroxylase (TH) was examined using immunohistochemistry and Western blot analysis. Results revealed that unilateral injection of 6-OHDA into the midbrain caused significant loss of TH positive cells in the substantia nigra, whereas rotigotine inhibited such loss of TH cells in 6-OHDA-induced mouse model of PD. In vitro experiments demonstrated that rotigotine increased expression levels of TH against 6-OHDA-induced toxicity. The expression level of TH after treatment with L’741,626, a D2 receptor antagonist was decreased more than that after treatment with GR 103691, a D3 receptor antagonist. These results suggest that rotigotine can protect DA neurons against 6-OHDA induced toxicity and that the protective effect of rotigotine for DAergic neurons through a DA D2 receptor is stronger than that through a DA D3 receptor.

Keyword

6-hydroxydopamine; dopamine D2 receptor; Parkinson’s disease; rotigotine; tyrosine hydroxylase
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