Reduction of voluntary physical activity in mice induced by toll-like receptor 7 agonist R-848

Abstract

The behavioral response of mice to infection is often demonstrated by a reduction in physical activity. Although it is known that single-stranded (ss) RNA, one of the genomes found in viruses, activates to produce type I interferon (IFNs) and pro-inflammatory cytokine via toll-like receptor (TLR) 7, the effect of TLR7 activation on spontaneous wheel-running activity is little known. To determine whether physical activity is regulated by TLR7 activation or not, we measured R-848 (which is a TLR7 agonist) -induced changes in spontaneous wheel-running activity in mice. Male C3H/HeN mice were IV injected with R-848 (0, 1 and 5 mg/kg), and their wheel-running activity was measured. Also, to clarify the effects of R-848-induced IFN-α, tumor necrosis factor (TNF)-α and prostaglandin (PG) E2 on wheel-running behavior, the R-848-injected wheel-running mice were treated with an inhibitor such as a neutralizing antibody specific to IFN-α, pentoxifylline (PTX) and indomethacin (IDM), respectively. It was observed that dose-dependent R-848 treatment reduced wheel-running activity, and the treatment induced an increase in plasma IFN-α, TNF-α, and PGE2 concentrations. However, the wheel-running activity was not attenuated by the anti-IFN-α antibody, PTX and IDM treatments. Our results suggest that the transient reduction in physical activity after R-848 injection is dose dependent, and that these phenomena might occur independently of the behavior caused by R-848-induced IFN-α, TNF-α and PGE2 via TLR7.

Keywords

• sickness behavior
• ifn-α
• tnf-α
• pge2