TY - JOUR
T1 - Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
AU - Miyata, Kohei
AU - Ikoma, Yoko
AU - Murata, Koshi
AU - Kusumoto-Yoshida, Ikue
AU - Kobayashi, Kenta
AU - Kuwaki, Tomoyuki
AU - Ootsuka, Youichirou
N1 - Funding Information:
The authors thank Ms Miki Sakoda at Kagoshima University and members of the Fukazawa laboratory and Life Science Research Laboratory at University of Fukui for technical assistance. We also thank Anna Antipov and Jett Zivkovic from Flinders University for proof reading. This research was supported by the Japan Society for the Promotion of Science KAKENHI Grant Number 23590280 to YO and 24390057 to TK, Japan and by Kodama Memorial Foundation for Medical Research to YO, Japan. Ootsuka and Kuwaki designed the research. Miyata, Ikoma and Ootsuka performed and analyzed all physiological recordings from animals. Murata, Kusumoto-Yoshida and Kobayashi performed the in situ hybridization experiment and its histological analysis. Miyata and Ootsuka drafted the manuscript. Miyata, Kuwaki and Ootsuka revised the manuscript. All authors have approved the final version of the manuscript and agreed to be accountable for all aspects of the work.
Funding Information:
The authors thank Ms Miki Sakoda at Kagoshima University and members of the Fukazawa laboratory and Life Science Research Laboratory at University of Fukui for technical assistance. We also thank Anna Antipov and Jett Zivkovic from Flinders University for proof reading. This research was supported by the Japan Society for the Promotion of Science KAKENHI Grant Number 23590280 to YO and 24390057 to TK, Japan and by Kodama Memorial Foundation for Medical Research to YO, Japan. Ootsuka and Kuwaki designed the research. Miyata, Ikoma and Ootsuka performed and analyzed all physiological recordings from animals. Murata, Kusumoto-Yoshida and Kobayashi performed the in situ hybridization experiment and its histological analysis. Miyata and Ootsuka drafted the manuscript. Miyata, Kuwaki and Ootsuka revised the manuscript. All authors have approved the final version of the manuscript and agreed to be accountable for all aspects of the work. This research was supported by the Japan Society for the Promotion of Science (KAKENHI) (23590280 to YO and 24390057 to TK) and by Kodama Memorial Foundation for Medical Research to YO. Ootsuka and Kuwaki designed the research. Miyata, Ikoma and Ootsuka performed and analyzed all physiological recordings from animals. Murata, Kusumoto-Yoshida and Kobayashi performed the in situ hybridization experiment and its histological analysis. Miyata and Ootsuka drafted the manuscript. Miyata, Kuwaki and Ootsuka revised the manuscript. All authors have approved the final version of the manuscript and agreed to be accountable for all aspects of the work.
Funding Information:
This research was supported by the Japan Society for the Promotion of Science (KAKENHI) (23590280 to YO and 24390057 to TK) and by Kodama Memorial Foundation for Medical Research to YO. Ootsuka and Kuwaki designed the research. Miyata, Ikoma and Ootsuka performed and analyzed all physiological recordings from animals. Murata, Kusumoto-Yoshida and Kobayashi performed the in situ hybridization experiment and its histological analysis. Miyata and Ootsuka drafted the manuscript. Miyata, Kuwaki and Ootsuka revised the manuscript. All authors have approved the final version of the manuscript and agreed to be accountable for all aspects of the work.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - Methamphetamine (METH), which is used to improve the alertness of narcoleptic patients, elicits autonomic physiological responses such as increases in body temperature, blood pressure and heart rate. We have shown that orexin synthesizing neurons, which have an important role in maintaining wakefulness, greatly contribute to the regulation of cardiovascular and thermoregulatory function. This regulation is partly mediated by glutamatergic as well as orexinergic signalling from the orexin neurons. These signals may also be involved in the autonomic response elicited by METH. This study aimed to determine if loss of either orexin or glutamate in orexin neurons would affect METH-induced changes in heart rate and body temperature. We used transgenic mice in which the vesicular glutamate transporter 2 gene was disrupted selectively in orexin-producing neurons (ORX;vGT2-KO), prepro-orexin knockout mice (ORX-KO), and control wild type mice (WT). We measured body temperature, heart rate and locomotor activity with a pre-implanted telemetry probe and compared the effect of METH (0.5, 2 and 5 mg/kg i.p.) on these parameters between these three groups. A low dose of METH induced hyperthermia and tachycardia responses in ORX;vGT2-KO mice, which were significant compared to ORX-KO and WT mice. The highest dose of METH induced hypothermia and bradycardia in ORX-KO mice, however, it induced hyperthermia in both WT and ORX;vGT2-KO mice. These results suggest that glutamate and orexin from orexin neurons have differential roles in mediating METH-induced changes in body temperature and heart rate.
AB - Methamphetamine (METH), which is used to improve the alertness of narcoleptic patients, elicits autonomic physiological responses such as increases in body temperature, blood pressure and heart rate. We have shown that orexin synthesizing neurons, which have an important role in maintaining wakefulness, greatly contribute to the regulation of cardiovascular and thermoregulatory function. This regulation is partly mediated by glutamatergic as well as orexinergic signalling from the orexin neurons. These signals may also be involved in the autonomic response elicited by METH. This study aimed to determine if loss of either orexin or glutamate in orexin neurons would affect METH-induced changes in heart rate and body temperature. We used transgenic mice in which the vesicular glutamate transporter 2 gene was disrupted selectively in orexin-producing neurons (ORX;vGT2-KO), prepro-orexin knockout mice (ORX-KO), and control wild type mice (WT). We measured body temperature, heart rate and locomotor activity with a pre-implanted telemetry probe and compared the effect of METH (0.5, 2 and 5 mg/kg i.p.) on these parameters between these three groups. A low dose of METH induced hyperthermia and tachycardia responses in ORX;vGT2-KO mice, which were significant compared to ORX-KO and WT mice. The highest dose of METH induced hypothermia and bradycardia in ORX-KO mice, however, it induced hyperthermia in both WT and ORX;vGT2-KO mice. These results suggest that glutamate and orexin from orexin neurons have differential roles in mediating METH-induced changes in body temperature and heart rate.
KW - Autonomic function
KW - Glutamate
KW - Orexin
KW - Thermoregulation
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=85123628604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123628604&partnerID=8YFLogxK
U2 - 10.1016/j.ibneur.2022.01.002
DO - 10.1016/j.ibneur.2022.01.002
M3 - Article
AN - SCOPUS:85123628604
SN - 2667-2421
VL - 12
SP - 108
EP - 120
JO - IBRO Neuroscience Reports
JF - IBRO Neuroscience Reports
ER -