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Striatal 5-HT1Areceptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat

Authors
Journal
Neuropharmacology
0028-3908
Publisher
Elsevier
Publication Date
Volume
55
Issue
8
Identifiers
DOI: 10.1016/j.neuropharm.2008.08.031
Keywords
  • 5-Ht1Areceptor
  • D1 Receptor
  • Dopamine
  • Dyskinesia
  • L-Dopa
  • Parkinson'S Disease
Disciplines
  • Medicine

Abstract

Abstract Convergent evidence suggests that serotonin 5-HT 1A receptor (5-HT 1AR) agonists reduce l-DOPA-induced dyskinesia by auto-regulating aberrant release of l-DOPA-derived dopamine (DA) from raphestriatal neurons. However, recent findings indicate that 5-HT 1AR stimulation also modifies D1 receptor (D1R)-mediated dyskinesia and rotations implicating a previously unexplored extra-raphe mechanism. In order to characterize the contribution of the striatum to these effects, rats with medial forebrain bundle DA lesions were tested for abnormal involuntary movements (AIMs) and rotations following striatal microinfusions of the 5-HT 1AR agonist ±8-OH-DPAT and systemic D1R agonist treatment with SKF81297. Additional rats with multi-site striatal DA lesions were tested for motor disability following systemic or intrastriatal ±8-OH-DPAT with or without systemic SKF81297. In rats with medial forebrain bundle lesions, striatal infusions of ±8-OH-DPAT dose-dependently reduced AIMs while conversely increasing rotations. In rats with striatal lesions, ±8-OH-DPAT alone, both systemic and intrastriatal administration, optimally reversed motor disability. Collectively, these results support an important functional interaction between 5-HT 1AR and D1R in the striatum with implications for the improved treatment of Parkinson's disease.

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