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The role of the dorsal raphe nucleus in the development, expression, and treatment of L ‐dopa‐induced dyskinesia in hemiparkinsonian rats
Author(s) -
Eskow Karen L.,
Dupre Kristin B.,
Barnum Christopher J.,
Dickinson Sando O.,
Park John Y.,
Bishop Christopher
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20630
Subject(s) - medial forebrain bundle , dorsal raphe nucleus , dopamine , raphe nuclei , neuroscience , serotonin , raphe , dyskinesia , forebrain , median raphe nucleus , parkinson's disease , biology , chemistry , endocrinology , medicine , striatum , receptor , serotonergic , central nervous system , disease
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. Synapse 63:610–620, 2009. © 2009 Wiley‐Liss, Inc.