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