title: Riluzole in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice.
abstract: BACKGROUND
  We previously demonstrated in mice that the activation of prelimbic medial prefrontal cortex (PL) with the sodium channel activator veratrine induces anxiety-like behaviors via NMDA receptor-mediated glutamatergic neurotransmission. Riluzole directly affects the glutamatergic system and has recently been suggested to have an anxiolytic-like effect in both experimental animals and patients with anxiety disorders.
  
  
  OBJECTIVE
  We investigated the effects of co-perfusion of riluzole on veratrine-induced anxiety-like behaviors in mice.
  
  
  METHODS
  Extracellular glutamate levels were measured in 7-week-old male C57BL6 mice by using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field (OF) test. Basal levels of glutamate were measured by collecting samples every 10 min for 60 min. The medium containing drugs was perfused for 30 min, and the OF test was performed during the last 10 min of drug perfusion. After the drug treatments, the drug-containing medium was switched to perfusion of control medium lacking drugs, and then samples were collected for another 90 min.
  
  
  RESULTS
  Riluzole co-perfusion attenuated veratrine-induced increase in extracellular glutamate levels in the PL and completely diminished veratrine-induced anxiety-like behaviors. Interestingly, riluzole perfusion alone in the PL did not affect the basal levels of glutamate and anxiety-like behaviors.
  
  
  CONCLUSIONS
  Our results suggest that compounds like riluzole that inhibit glutamatergic function in the PL are possible candidates for novel anxiolytics.
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo, 187-8553, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ohashi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Oka
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D014702:Veratrine / Q000633:toxicity*
chemical_list: D014151:Anti-Anxiety Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D019782:Riluzole; D014702:Veratrine