These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Behavioral and cellular dopamine D1 and D3 receptor-mediated synergy: Implications for L-DOPA-induced dyskinesia.
    Author: Lanza K, Meadows SM, Chambers NE, Nuss E, Deak MM, Ferré S, Bishop C.
    Journal: Neuropharmacology; 2018 Aug; 138():304-314. PubMed ID: 29936243.
    Abstract:
    Individually, D1 and D3 dopamine receptors (D1R and D3R, respectively) have been implicated in L-DOPA-induced dyskinesia (LID). Of late, direct D1R-D3R interactions have been linked to LID yet remain enigmatic. Therefore, the current research sought to characterize consequences of putative D1R-D3R interactions in dyskinesia expression and in LID-associated downstream cellular signaling. To do so, adult male Sprague-Dawley hemi-parkinsonian rats were given daily L-DOPA (6 mg/kg; s.c.) for 2 weeks to establish stable LID, as measured via the abnormal voluntary movements (AIMs) scale. Thereafter, rats underwent dose-response AIMs testing for the D1R agonist SKF38393 (0, 0.3, 1.0, 3.0 mg/kg) and the D3R agonist, PD128907 (0, 0.1, 0.3, 1.0 mg/kg). Each agonist dose-dependently induced dyskinesia, implicating individual receptor involvement. More importantly, when threshold doses were co-administered, rats displayed synergistic exacerbation of dyskinesia. Interestingly, this observation was not mirrored in general locomotor behaviors, highlighting a potentially dyskinesia-specific effect. To illuminate the mechanisms by which D1R-D3R co-stimulation led to in vivo synergy, levels of striatal phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were quantified after administration of SKF38393 and/or PD128907. Combined agonist treatment synergistically drove striatal pERK1/2 expression. Together, these results support the presence of a functional, synergistic interaction between D1R and D3R that manifests both behaviorally and biochemically to drive dyskinesia in hemi-parkinsonian rats.
    [Abstract] [Full Text] [Related] [New Search]