Hiroko Fukunaga (1), Masakatsu Takahashi (1,*), Hiroshi Kaneto (2) and
Masaaki Yoshikawa (3)
(1) Department of Pharmacoinformatics, School of Pharmaceutical Sciences, Nagasaki University, (2) Emeritus Professor, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
(3) Research Institute for Food Sciences, Kyoto University, Uji, Kyoto 611-0011, Japan
(*) To whom correspondence should be addressed.
Abstract: The role of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in biological responses to stress exposure was examined in mice. Intraperitoneal or intracerebroventricular administration of Tyr-MIF-1 attenuated not only footshock (FS)- and forced swimming (SW)-stress-induced analgesia (SIA) but also socio-psychological (PSY)-SIA that, when using the communication box, is produced without any direct physical nociceptions. Tyr-Mif-1 also disrupted the suppressive effect of concurrent exposure to FS- and PSY-stress on the development of morphine antinociceptive tolerance. In elevated-plus-maze tests, mice treated with Tyr-MIF-1 tended to spend more time in the open arms compared with the control group, suggesting the anxiolytic properties of the peptide. Thus, the finding that Tyr-MIF-1 modulates these stress responses suggests that the peptide regulates an endogenous biological alert system responding to stress exposure, perhaps, counteracting the excessive response of the system. Furthermore, Tyr-MIF-1, in the case of PSY-stress, through the attenuation of emotional factors such as fear and anxiety, may suppress PSY-SIA and inhibition by PSY-stress of the development of morphine tolerance.
Keywords: Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Stress-induced analgesia (SIA), Morphine tolerance, Emotionality, Socio-psychological stress