Research article summary (published 29 Jun 2009):

The role of the dorsal raphe nucleus in the development, expression, and treatment of L-dopa-induced dyskinesia in hemiparkinsonian rats.

Full Abstract

Convergent evidence indicates that in later stages of Parkinson's disease raphestriatal serotonin neurons compensate for the loss of nigrostriatal dopamine neurons by converting and releasing dopamine derived from exogenous administration of the pharmacotherapeutic L-3,4-dihydroxyphenyl-L-alanine (L-dopa). Because the serotonin system is not equipped with dopamine autoregulatory mechanisms, it has been postulated that raphe-mediated striatal dopamine release may fluctuate dramatically. These fluctuations may portend the development of abnormal involuntary movements called L-dopa-induced dyskinesia (LID). As such, it has been hypothesized that reducing the activity of raphestriatal neurons could dampen supraphysiological stimulation of striatal dopamine receptors thereby alleviating LID. To directly address this, the current study employed the rodent model of LID to investigate the contribution of the rostral raphe nuclei (RRN) in the development, expression and treatment of LID. In the first study, dual serotonin/dopamine selective lesions of the RRN and medial forebrain bundle, respectively, verified that the RRN are essential for the development of LID. In a direct investigation into the neuroanatomical specificity of these effects, microinfusions of +/-8-OH-DPAT into the intact dorsal raphe nucleus dose-dependently attenuated the expression of LID without affecting the antiparkinsonian efficacy of L-dopa. These current findings reveal the integral contribution of the RRN in the development and expression of LID and implicate a prominent role for dorsal raphe 5-HT1AR in the efficacious properties of 5-HT1AR agonists.

Author information

Author/s: Eskow, Karen L (KL); Dupre, Kristin B (KB); Barnum, Christopher J (CJ); Dickinson, Sando O (SO); Park, John Y (JY); Bishop, Christopher (C);

Affiliation: Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, New York 13902-6000, USA.

Grants: NS059600 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Synapse (New York, N.Y.) (Synapse), published in United States. (Language: eng)

Reference: 2009-Jul; vol 63 (issue 7) : pp 610-20

Dates: Created 2009/05/12; Completed 2009/08/13; Revised 2009/09/14;

PMID: 19309758, status: MEDLINE (last retrieval date: 9/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

3,4-Dihydroxyphenylacetic Acid - metabolism Animals Corpus Striatum - metabolism Dopamine - metabolism Dyskinesia, Drug-Induced - physiopathology Hydroxyindoleacetic Acid - metabolism Levodopa Male Medial Forebrain Bundle - drug effects; physiopathology

Medial Forebrain Bundle - drug effects; physiopathology Motor Activity - drug effects Neurons - drug effects; metabolism Raphe Nuclei - drug effects; physiopathology Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT1A - metabolism Serotonin - metabolism Serotonin Agents - pharmacology

Associated Chemicals: Levodopa (0) ; Serotonin Agents (0) ; 3,4-Dihydroxyphenylacetic Acid (102-32-9) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Serotonin (50-67-9) ; Hydroxyindoleacetic Acid (54-16-0)

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