Capsaicin (CAP), the pungent ingredient of hot red pepper, is a selective ligand for the heat-sensitive transient receptor potential V1 cation channel 1 (TRPV1). Although CAP has been traditionally used as the ingredient of spices for various foods in the world, the effect of oral intake of CAP on thermoregulation and locomotor activity, and CAP-induced activation of brain neural circuits are not well understood. In this study, therefore, we examined the effects of oral gavage of CAP on core body and tail surface temperature, locomotor activity, and Fos expression in thermoregulation- and sensory information-associated hypothalamic and medullary brain regions using freely moving mice. Oral gavage of CAP acutely decreased core body temperature and alternatively increased tail surface temperature of wild type (WT) mice, whereas such acute temperature changes were not observed in TRPV1 knockout (KO) animals Moreover, a long-lasting increase of locomotor activity was observed in both WT and TRPV1 KO mice after oral gavage of CAP, but increage in core body temperature was seen only in TRPV1 KO animals. Oral gavage of CAP induced neuronal Fos expression in the circumventricular organs, median and medial preoptic area, arcuate nucleus, and nucleus of the solitary tract, whereas neuronal Fos expression was scarcely observed in TRPV1 KO mice. Thus, the present study demonstrates in the mice that oral intake of CAP causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity, and moreover activates the brain circuits controlling thennoregulation and metabolism.
