Journal ArticleDOI
Brain 5-HT(2A) receptors in MPTP monkeys and levodopa-induced dyskinesias.
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The results confirm the involvement of serotonergic pathways and the glutamate/serotonin interactions in LID and support targeting 5‐HT2A receptors as a potential treatment for LID.Abstract:
Levodopa-induced dyskinesias (LIDs) are abnormal involuntary movements induced by the chronic use of levodopa (l-Dopa) limiting the quality of life of Parkinson's disease (PD) patients. We evaluated changes of the serotonin 5-HT(2A) receptors in control monkeys, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys and in l-Dopa-treated MPTP monkeys, without or with adjunct treatments to inhibit the expression of LID: CI-1041, a selective NR1A/2B subunit antagonist of glutamate N-methyl-d-aspartic acid (NMDA) receptor, or Cabergoline, a long-acting dopamine D(2) receptor agonist. All treatments were administered for 1 month and animals were killed 24 h after the last dose of l-Dopa. Striatal concentrations of serotonin were decreased in all MPTP monkeys investigated, as measured by high-performance liquid chromatography. [(3) H]Ketanserin-specific binding to 5-HT(2A) receptors was measured by autoradiography. l-Dopa treatment that induced dyskinesias increased 5-HT(2A) receptor-specific binding in the caudate nucleus and the anterior cingulate gyrus (AcgG) compared with control monkeys. Moreover, [(3) H]Ketanserin-specific binding was increased in the dorsomedial caudate nucleus in l-Dopa-treated MPTP monkeys compared with saline-treated MPTP monkeys. Nondyskinetic monkeys treated with CI-1041 or Cabergoline showed low 5-HT(2A) -specific binding in the posterior dorsomedial caudate nucleus and the anterior AcgG compared with dyskinetic monkeys. No significant difference in 5-HT(2A) receptor binding was observed in any brain regions examined in saline-treated MPTP monkeys compared with control monkeys. These results confirm the involvement of serotonergic pathways and the glutamate/serotonin interactions in LID. They also support targeting 5-HT(2A) receptors as a potential treatment for LID.read more
Citations
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Journal ArticleDOI
The serotonergic system in Parkinson's disease.
TL;DR: All published preclinical and clinical studies that have investigated the serotonergic system in PD and related animal models are summarized and discussed in order to recapitulate the state of the current knowledge and to identify areas that need further research and understanding.
Journal ArticleDOI
Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease
Cristina Miguelez,Teresa Morera-Herreras,María Torrecilla,José Ángel Ruiz-Ortega,Luisa Ugedo +4 more
TL;DR: An overview of serotonergic modulation of the BG at the functional level is provided and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA is discussed.
Journal ArticleDOI
The serotonergic system in motor and non-motor manifestations of Parkinson’s disease
Philippe Huot,Susan H. Fox +1 more
TL;DR: Critically reviews studies assessing the SERT, as well as 5-HT1A and 5- HT2A receptors in idiopathic PD and animal models of PD, and discusses unmet challenges to effectively treat manifestations of PD using SERT antagonists, 5-ht1A agonists and5-HT2A antagonists.
Journal ArticleDOI
Metabotropic glutamate receptors for Parkinson's disease therapy.
TL;DR: The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD.
Journal ArticleDOI
Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia.
TL;DR: The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain, and opens an important reserve of possible strategies to limit LIDs.
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