title: 5-HT1A receptor-dependent control of nigrostriatal dopamine neurotransmission in the pharmacotherapy of Parkinson's disease and schizophrenia.
abstract: Dysfunctions of the basal ganglia are associated with a number of neurological and psychiatric conditions including Parkinson's disease and schizophrenia. Current treatments of these disorders are mostly symptomatic and inadequate, and are often associated with a number of unwanted side-effects. The striatum, the terminal region of the nigrostriatal dopamine pathway, is the main input nucleus of the basal ganglia, and dopamine neurotransmission through the nigrostriatal pathway plays a crucial role in the modulation of basal ganglia output and mediated behaviors. Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the modulation of dopamine neurotransmission and in improving pharmacotherapy in schizophrenia and Parkinson's disease. This review concerns the role of 5-HT1A receptors in the modulation of nigrostriatal dopamine neurotransmission, with the aim of providing guidelines for future research to improve pharmacotherapy. The current state of knowledge suggests that drugs simultaneously targeting dopamine D2 and 5-HT1A receptors may improve pharmacotherapy for schizophrenia and Parkinson's disease. Activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus has an important role in the alleviation of extrapyramidal symptoms and levodopa-induced dyskinesia induced by antipsychotic treatment. Drugs acting exclusively through dopamine D2 and 5-HT1A receptors are highly needed to validate the potential role of 5-HT1A receptors in improving therapeutics for Parkinson's disease and schizophrenia.
authors.affiliation: Neuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi, Pakistan.
authors.forename: Darakhshan J
authors.initials: DJ
authors.lastname: Haleem
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology; D001479:Basal Ganglia / Q000473:pathology*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A; D004298:Dopamine