Haleem Darakhshan J
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.
Behav Pharmacol. 2015 Feb;26(1-2):45-58. doi: 10.1097/FBP.0000000000000123.
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.
基底神经节功能障碍与包括帕金森病和精神分裂症在内的多种神经和精神疾病有关。目前对这些疾病的治疗大多只是对症治疗且效果不佳，并且常常伴有许多不良副作用。纹状体是黑质纹状体多巴胺通路的终末区域，是基底神经节的主要输入核，通过黑质纹状体通路的多巴胺神经传递在调节基底神经节输出和介导行为方面起着关键作用。有证据表明5-羟色胺（5-HT；血清素）-1A受体在调节多巴胺神经传递以及改善精神分裂症和帕金森病的药物治疗方面发挥作用。本综述关注5-HT1A受体在调节黑质纹状体多巴胺神经传递中的作用，旨在为未来改善药物治疗的研究提供指导。目前的知识状况表明，同时靶向多巴胺D2和5-HT1A受体的药物可能会改善精神分裂症和帕金森病的药物治疗。中缝背核中树突体5-HT1A受体的激活在减轻抗精神病药物治疗引起的锥体外系症状和左旋多巴诱导的运动障碍方面具有重要作用。迫切需要仅通过多巴胺D2和5-HT1A受体起作用的药物来验证5-HT1A受体在改善帕金森病和精神分裂症治疗方面的潜在作用。
