title: Methamphetamine modulates glutamatergic synaptic transmission in rat primary cultured hippocampal neurons.
abstract: Methamphetamine (METH) is a psychostimulant drug. Abuse of METH produces long-term behavioral changes including behavioral, sensitization, tolerance, and dependence. It induces neurotoxic effects in several areas of the brain via enhancing dopamine (DA) level abnormally, which may cause a secondary release of glutamate (GLU). However, repeated administration of METH still increases release of GLU even when dopamine content in tissue is significantly depleted. It implies that some other mechanisms are likely to involve in METH-induced GLU release. The goal of this study was to observe METH affected glutamatergic synaptic transmission in rat primary cultured hippocampal neurons and to explore the mechanism of METH modulated GLU release. Using whole-cell patch-clamp recordings, we found that METH (0.1-50.0μM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs). However, METH decreased the frequency of sEPSCs and mEPSCs at high concentration of 100μM. The postsynaptic NMDA receptor currents and P/Q-type calcium channel were not affected by the use of METH (10,100μM). METH did not present visible effect on N-type Ca(2+) channel current at the concentration lower than 50.0μM, but it was inhibited by use of METH at a 100μM. The effect of METH on glutamatergic synaptic transmission was not revered by pretreated with DA receptor antagonist SCH23390. These results suggest that METH directly modulated presynaptic GLU release at a different concentration, while dopaminergic system was not involved in METH modulated release of GLU in rat primary cultured hippocampal neurons.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Shuzhuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Yuelei
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Lujia
authors.initials: L
authors.lastname: Yang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Zhi juan
authors.initials: Zj
authors.lastname: Ge
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850. Electronic address: jinli9802@yahoo.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Street, Beijing 100850. Electronic address: zhengjq@bmi.ac.cn.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D008694:Methamphetamine / Q000494:pharmacology*; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001552:Benzazepines; D020864:Calcium Channels, N-Type; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; D018698:Glutamic Acid; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Excitatory postsynaptic currents; Hippocampal neurons; Methamphetamine; Whole-cell recording