title: Systemic administration of riluzole enhances recognition memory and facilitates extinction of fear memory in rats.
abstract: Strategies to enhance recognition memory and facilitate extinction of fear memory have attracted increasing attention for enhancing the effectiveness of exposure therapy for anxiety disorders. Previously, we demonstrated that systemic administration of riluzole has clear anxiolytic-like effects, without impairing memory, in rats. In the present study, we examined whether riluzole could have therapeutic potential for anxiety disorders when combined with exposure therapy. Both riluzole and D-cycloserine enhanced recognition memory in the novel object recognition test and facilitated extinction learning in the contextual fear conditioning in rats. Interestingly, the facilitatory effect of riluzole on extinction learning was clearly observed even after a short re-exposure to the context, while D-cycloserine was ineffective at facilitating extinction when a short duration exposure session was given. In contrast, diazepam impaired both recognition memory and the extinction of fear memory. Our findings strongly suggest that systemic administration of riluzole may have therapeutic efficacy when combined with exposure therapy for treating a range of anxiety disorders. Clinical trials to examine the efficacy of riluzole in combination with exposure therapy in these patients are warranted.
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Sugiyama
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Oka
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan. Electronic address: mitsu@ncnp.go.jp.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D003523:Cycloserine / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D017208:Rats, Wistar; D019782:Riluzole / Q000008:administration & dosage*
chemical_list: D011619:Psychotropic Drugs; D019782:Riluzole; D003523:Cycloserine
keywords: Exposure therapy; Extinction; Fear conditioning; Recognition memory; Riluzole; d-cycloserine