title: Pathophysiological roles of serotonergic system in regulating extrapyramidal motor functions.
abstract: The serotonergic nervous system plays crucial roles in regulating psycho-emotional, cognitive, sensori-motor and autonomic functions. It is now known that multiple serotonin (5-hydroxytryptamine; 5-HT) receptors regulate extrapyramidal motor functions, which are implicated in pathogenesis and/or treatment of various neurological disorders (e.g., Parkinson's disease and drug-induced extrapyramidal motor deficits). Specifically, antagonism of 5-HT2A/2C receptors alleviates antipsychotic-induced extrapyramidal side effects (EPS) by relieving the 5-HT2A/2C receptor-mediated inhibition of nigral dopaminergic neuron activity and striatal dopamine release. Indeed, many of the second generation antipsychotics (e.g., risperidone, perospirone and olanzapine) commonly possess potent 5-HT2A/2C blocking actions which contribute to their atypical antipsychotic property. In addition, activation of 5-HT1A receptors also improves antipsychotic-induced EPS and motor disabilities in animal models of Parkinson's disease. Microinjection studies revealed that stimulation of postsynaptic 5-HT1A receptors in the striatum or motor cortex plays an important role in the antiparkinsonian actions. Furthermore, recent studies demonstrated that antagonism of 5-HT3 and 5-HT6 receptors alleviates extrapyramidal motor disorders while 5-HT4, 5-HT5, and 5-HT7 receptors are mostly inactive. These results encourage drug discovery research into new 5-HT receptor ligands that could improve current therapies for extrapyramidal motor disorders.
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ohno
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokudome
mesh_terms: D000818:Animals; D001480:Basal Ganglia Diseases / Q000503:physiopathology*; D006801:Humans; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin