Role of the primary motor cortex in L-DOPA-induced dyskinesia and its modulation by 5-HT1A receptor stimulation

NEUROPHARMACOLOGY

卷:61

Article

Ostock, Corinne Y.¹  Dupre, Kristin B.¹  Jaunarajs, Karen L. Eskow¹  Walters, Hannah¹  George, Jessica¹  Krolewski, David²  Walker, Paul D.²  Bishop, Christopher¹ 

[1] SUNY Binghamton, Dept Psychol, Behav Neurosci Program, Binghamton, NY 13902 USA

[2] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA

关键词: Primary motor cortex;    Parkinson's disease;    L-DOPA-induced dyskinesia;    Serotonin;    c-Fos;   

DOI  :  10.1016/j.neuropharm.2011.05.021

来源: Elsevier

【 摘 要 】

While serotonin 5-HT1A receptor (5-HT1AR) agonists reduce L-DOPA-induced dyskinesias (LID) by normalizing activity in the basal ganglia neurocircuitry, recent evidence suggests putative 5-HT1AR within the primary motor cortex (M1) may also contribute. To better characterize this possible mechanism, c-fos immunohistochemistry was first used to determine the effects of systemic administration of the full 5-HT1AR agonist +/-8-OH-DPAT on L-DOPA-induced immediate early gene expression within M1 and the prefrontal cortex (PFC) of rats with unilateral medial forebrain bundle (MFB) dopamine (DA) lesions. Next, in order to determine if direct stimulation of 5-HT1AR within M1 attenuates the onset of LID, rats with MFB lesions were tested for L-DOPA-induced abnormal involuntary movements (AIMs) and rotations following M1 microinfusions of +/-8-OH-DPAT with or without coadministration of the 5-HT1AR antagonist WAY100635. Finally, +/-8-OH-DPAT was infused into M1 at peak dyskinesia to determine if 5-HT1AR stimulation attenuates established L-DOPA-induced AIMs and rotations. While no treatment effects were seen within the PFC. systemic +/-8-OH-DPAT suppressed L-DOPA-induced c-fos within M1. Intra-M1 5-HT1AR stimulation diminished the onset of AIMs and this effect was reversed by WAY100635 indicating receptor specific effects. Finally, continuous infusion of +/-8-OH-DPAT into M1 at peak dyskinesia alleviated L-DOPA-induced AIMs. Collectively, these findings support an integral role for M1 in LID and its modulation by local 5-HT1AR. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

Free