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Changes on 5-HT2 receptor mRNAs in striatum and subthalamic nucleus in Parkinson's disease model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
2007 (English)In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 92, no 1-2, 29-33 p.Article in journal (Refereed) Published
Abstract [en]

Changes on 5-HT2 receptor mRNAs in striatum and subthalamic nucleus in Parkinson's disease model. PHYSIOL. BEHAV. 00(0), 000-000, 2006. Abnormal interactions between the serotonin and dopamine systems may underlie the high prevalence of non-motor complications in Parkinson's disease (PD). Here, we demonstrate that the genes encoding serotonin 5-HT2A and 5-HT2C receptors are differently regulated by dopamine in the 6-hydroxydopamine (6-OHDA) rat model of PD. Nigrostriatal cell loss causes an up-regulation of 5-HT2AR mRNA, but a down-regulation of 5-HT2CR mRNA, in striatum. Repeated injections with L-DOPA/benserazide reverse the effect of 6-OHDA lesioning on 5-HT2AR, but not on 5-HT2CR, gene expression. Neither 6-OHDA-lesioning nor L-DOPA/benserazide treatment had any effect on 5-HT2AR mRNA in cortex or on 5-HT2CR mRNA in nucleus subthalamicus. These data suggest that the regulation of 5-HT2AR in striatum, in the 6-OHDA rat model of PD, is mainly dependent upon alterations in dopamine levels. 5-HT2CR, on the other hand, are regulated by nigrostriatal cell loss and by the accompanied reduction of factor(s), other than dopamine, that are normally co-expressed with dopamine. The apparent imbalance between 5-HT2AR and 5-HT2CR levels in this PD model indicates a potential role for these receptors in the pathophysiology of neuropsychiatric symptoms, such as depression and L-DOPA-induced hallucinations, which are co-morbid with PD. The fact that 5-HT2CR are differentially regulated as compared to 5-HT2AR to alterations in the dopamine tone predicts that pharmacological manipulations at 5-HT2CR, but not at 5-HT2AR, will result in similar effects in PD patients whether they are treated or not with dopamine replacement.

Place, publisher, year, edition, pages
2007. Vol. 92, no 1-2, 29-33 p.
Keyword [en]
Serotonin, Parkinson's disease, 5-HT2 receptor, Striatum, Nucleus subthalamicus
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-103585DOI: 10.1016/j.physbeh.2007.05.033ISI: 000250099600007PubMedID: 17588622OAI: oai:DiVA.org:uu-103585DiVA: diva2:218513
Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2011-01-20Bibliographically approved

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