title: Pseudoginsenoside-F11 inhibits methamphetamine-induced behaviors by regulating dopaminergic and GABAergic neurons in the nucleus accumbens.
abstract: BACKGROUND
  Although dependence to methamphetamine (METH) is associated with serious psychiatric symptoms and is a global health and social problem, no effective therapeutic approaches have been identified. Pseudoginsenoside-F11 (PF11) is an ocotillol-type saponin that is isolated from Panax quinquefolius (American ginseng) and was shown to have neuroprotective effects to promote learning and memory and to antagonize the pharmacological effects of morphine. Furthermore, PF11 also shows protective effects against METH-induced neurotoxicity in mice. However, the effects of PF11 on METH-induced preference and dopamine (DA) release have not been defined.
  
  
  OBJECTIVE
  We investigated the effects of PF11 administration on METH-induced hyperlocomotion and conditioned place preference (CPP) in mice. Subsequently, extracellular DA and gamma-aminobutyric acid (GABA) levels were determined in the nucleus accumbens (NAc) of mice after co-administration of PF11 and METH using in vivo microdialysis analyses. Moreover, the effects of PF11 administration on the μ-opioid neuronal responses, DAMGO (μ-opioid receptor agonist; [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin)-induced hyperlocomotion and accumbal extracellular DA increase were investigated to elucidate how PF11 inhibits METH-induced dependence by dopaminergic neuronal hyperfunction.
  
  
  RESULTS
  Co-administration of PF11 and METH for 6 days attenuated METH-induced locomotor sensitization compared with treatment with METH alone. In the CPP test, PF11 administration also inhibited METH-induced place preference. In vivo microdialysis analyses indicated that co-administration of PF11 and METH for 7 days prevented METH-induced extracellular DA increase in the NAc and repeated PF11 administration with or without METH for 7 days increased extracellular GABA levels in the NAc, whereas single administration of PF11 did not. Furthermore, DAMGO-induced hyperlocomotion and accumbal extracellular DA increase were significantly inhibited by acute PF11 administration.
  
  
  CONCLUSIONS
  The present data suggest that PF11 inhibits METH-induced hyperlocomotion, preference, and accumbal extracellular DA increase by regulating GABAergic neurons and μ-opioid receptors.
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
authors.forename: Kequan
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.|Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Huiyang
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan. nitta@pha.u-toyama.ac.jp.
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D036145:Ginsenosides; D017450:Receptors, Opioid, mu; C413985:pseudoginsenoside F11; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D004298:Dopamine
keywords: Dopamine; GABA; Methamphetamine; Microdialysis; Nucleus accumbens; Pseudoginsenoside-F11; μ-opioid receptors