Serotonin 1B receptor stimulation reduces D1 receptor agonist-induced dyskinesia

Academic Article

Abstract

  • Dopamine replacement therapy for the treatment of Parkinsons disease leads to deleterious abnormal involuntary movements (AIMs), known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, which parallels enhanced striatal dopamine D1 receptor-mediated signaling. Recent evidence suggests stimulation of striatal serotonin (5-HT) 1B receptors may reduce D1-mediated signaling. Given this potential antidyskinetic mechanism, male hemiparkinsonian Sprague-Dawley rats received treatments of D1 receptor agonist, SKF81297, (0.8mg/kg) or L-DOPA (12mg/kg, subcutaneous injection). Dyskinetic movements were rated using the AIMs scale. Rats were then administered vehicle (100% dimethyl sulfoxide) or the 5-HT1B receptor agonist, CP94253, (1.5 or 3.0mg/kg, subcutaneous injection), followed by SKF81297 or L-DOPA and rated for AIMs. Results indicate that CP94253 mitigates both L-DOPA and D1 receptor agonist-induced dyskinesia. These findings suggest that 5-HT1B receptor stimulation directly diminishes D1 receptor-mediated dyskinesia, implicating an important target for the treatment of L-DOPA-induced dyskinesia. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
  • Authors

    Published In

  • NeuroReport  Journal
  • Digital Object Identifier (doi)

    Author List

  • Eskow Jaunarajs KL; Dupre KB; Steiniger A; Klioueva A; Moore A; Kelly C; Bishop C
  • Start Page

  • 1265
  • End Page

  • 1269
  • Volume

  • 20
  • Issue

  • 14