title: The pyramidal neurons in the medial prefrontal cortex show decreased response to 5-hydroxytryptamine-3 receptor stimulation in a rodent model of Parkinson's disease.
abstract: In the present study, effect of SR 57227A, a selective 5-hydroxytryptamine-3 (5-HT(3)) receptor agonist, on the firing activity of pyramidal neurons in the medial prefrontal cortex (mPFC) was studied in normal rats and rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta by using extracellular recording. Systemic administration of SR 57227A (40-640 μg/kg, i.v.) decreased the mean firing rate of pyramidal neurons in normal and the lesioned rats. This inhibition was significant only at doses higher than 320 μg/kg and 640 μg/kg in normal and the lesioned rats, respectively, and was reversed by i.v. administration of 5-HT(3) receptor antagonist tropisetron or GABA(A) receptor antagonist bicuculline. Furthermore, local application of SR 57227A (0.01 μg) in the mPFC inhibited the firing rate of pyramidal neurons in normal rats while having no effect on firing rate in the lesioned rats. The i.v. administration of bicuculline excited the pyramidal neurons in normal rats, and then local application of SR 57227A did not alter the mean firing rate of these neurons. However, these two drugs did not affect the activity of the pyramidal neurons in the lesioned rats. We conclude that activation of 5-HT(3) receptors inhibited pyramidal neurons in the mPFC of normal rats via GABAergic interneurons, and degeneration of the nigrostriatal pathway decreased response of the pyramidal neurons to SR 57227A, suggesting the dysfunction of 5-HT(3) receptors and/or down-regulation of the expression on GABAergic interneurons in the lesioned rats.
authors.affiliation: Department of Encephalopathy, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China. zhangqj@mail.xjtu.edu.cn
authors.forename: Qiao Jun
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Li Bo
authors.initials: LB
authors.lastname: Li
authors.forename: Xiao Lin
authors.initials: XL
authors.lastname: Niu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Zhen Hua
authors.initials: ZH
authors.lastname: Gui
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Feng
authors.forename: Umar
authors.initials: U
authors.lastname: Ali
authors.forename: Yan Pin
authors.initials: YP
authors.lastname: Hui
authors.forename: Zhong Heng
authors.initials: ZH
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology*; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000473:pathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000473:pathology; D000077526:Tropisetron; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D058787:GABA-A Receptor Antagonists; D007211:Indoles; D010880:Piperidines; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D000077526:Tropisetron; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride; D004298:Dopamine; D001640:Bicuculline