title: Chronic haloperidol increases voltage-gated Na+ currents in mouse cortical neurons.
abstract: Typical antipsychotics are characterized by extrapyramidal syndrome (EPS). Previous studies demonstrated that typical antipsychotics could inhibit neuronal voltage-gated sodium channel (VGSC). However, EPS typically emerge only upon prolonged exposure. As a result, we examined effects of haloperidol, a prototype typical antipsychotic, on neuronal VGSC upon incubation for varying duration. Briefly, VGSC currents were activated and recorded using a whole-cell patch-clamp technique in primary culture of mouse cortical neurons. VGSC activity was inhibited by acute haloperidol exposure (for minutes), but enhanced in a time- and concentration-dependent manner by chronic haloperidol exposure (for hours). The effects of chronic haloperidol were associated with increased expression of VGSC subunits as well as corresponding electrophysiological channel properties. In summary, we found enhanced VGSC currents upon chronic haloperidol exposure in cortical neurons in contrast to inhibition by acute haloperidol exposure. Such a results may contribute to EPS of typical antipsychotics.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, Guangdong 515041, China; Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, Guangdong 515041, China.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China. Electronic address: ksli@stu.edu.cn.
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D006220:Haloperidol / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D061566:Voltage-Gated Sodium Channels; D012964:Sodium; D006220:Haloperidol
keywords: BDNF; Bromocriptine; Cortical neurons; Haloperidol; Patch-clamp recording; Voltage-gated sodium channels