title: Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression.
abstract: Others and we have reported that rhynchophylline reverses amphetamine-induced conditioned place preference (CPP) effect which may be partly mediated by amelioration of central neurotransmitters and N-methyl-d-aspartate receptor 2B (NR2B) levels in the rat brains. The current study investigated the inhibiting effects of rhynchophylline on methamphetamine-induced (METH-induced) CPP in adult zebrafish and METH-induced locomotor activity in tyrosine hydroxylase-green fluorescent protein (TH-GFP) transgenic zebrafish larvae and attempted to confirm the hypothesis that these effects were mediated via regulation of neurotransmitters and dopaminergic and glutamatergic systems. After baseline preference test (on days 1-3), zebrafish were injected intraperitoneally METH (on days 4, 6 and 8) or the same volume of fish physiological saline (on days 5 and 7) and were immediately conditioned. Rhynchophylline was administered at 12h after injection of METH. On day 9, zebrafish were tested for METH-induced CPP. Results revealed that rhynchophylline (100mg/kg) significantly inhibited the acquisition of METH-induced CPP, reduced the content of dopamine and glutamate and down-regulated the expression of TH and NR2B in the CPP zebrafish brains. Furthermore, the influence of rhynchophylline on METH-induced locomotor activity was also observed in TH-GFP transgenic zebrafish larvae. Results showed that rhynchophylline (50mg/L) treatment led to a significant reduction on the locomotor activity and TH expression in TH-GFP transgenic zebrafish larvae. Taken together, these data indicate that the inhibition of the formation of METH dependence by rhynchophylline in zebrafish is associated with amelioration of the neurotransmitters dopamine and glutamate content and down-regulation of TH and NR2B expression.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Mingjin
authors.initials: M
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Guilin Medical University, Guilin 541004, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Qiuxian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Fang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Shenzhen Seventh People's Hospital, Shenzhen 518081, China.
authors.forename: Qunzhao
authors.initials: Q
authors.lastname: Kang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Ken Kin Lam
authors.initials: KK
authors.lastname: Yung
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: cherrymo_smu@126.com.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Mo
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D008694:Methamphetamine / Q000009:adverse effects*; D000078183:Oxindoles; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish
chemical_list: D026121:Indole Alkaloids; C121001:NR2B NMDA receptor; D000078183:Oxindoles; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008694:Methamphetamine; C052714:rhyncophylline; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Methamphetamine dependence; NR2B; Neurotransmitters; Rhynchophylline; TH