title: Toll-like receptor 7-mediated enhancement of contextual fear memory in mice.
abstract: Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers production of the type I interferons (IFNs) IFN-α and IFN-β. Imiquimod, a synthetic TLR7 ligand, induces production of type I IFNs and is used clinically as an antiviral and antitumor drug. In the present study, we examined the effect of imiquimod on conditioned and innate fear behaviors in mice. Imiquimod was administered 2, 4, or 15 h before contextual fear conditioning. Imiquimod treatment 4 or 15 h before fear conditioning significantly enhanced context-dependent freezing behavior. This imiquimod-induced enhancement of fear-related behaviors was observed 120 h after fear conditioning. In contrast, imiquimod failed to enhance context-dependent freezing behavior in TLR7 knockout mice. Imiquimod had no significant effect on pain threshold or on innate fear-related behavior, as measured by the elevated plus-maze. The levels of type I IFN mRNA in the brain were significantly increased at 2 h after imiquimod treatment. Imiquimod also increased interleukin (IL)-1β mRNA expression in the brain at 4 h following administration, while mRNA expression of F4/80, a macrophage marker, was unaffected by imiquimod treatment. Our findings suggest that TLR7-mediated signaling enhances contextual fear memory in mice, possibly by inducing the expression of type I IFNs and IL-1β in the brain.
authors: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
authors: Yasunori
authors: Y
authors: Kubo
authors: Yoshiki
authors: Y
authors: Yanagawa
authors: Machiko
authors: M
authors: Matsumoto
authors: Sachiko
authors: S
authors: Hiraide
authors: Masanobu
authors: M
authors: Kobayashi
authors: Hiroko
authors: H
authors: Togashi
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D005239:Fear; D000077271:Imiquimod; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000502:physiology*
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D051199:Toll-Like Receptor 7; D000077271:Imiquimod