Cargando…

Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate

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 wakefuln...

Descripción completa

Detalles Bibliográficos
Autores principales: Miyata, Kohei, Ikoma, Yoko, Murata, Koshi, Kusumoto-Yoshida, Ikue, Kobayashi, Kenta, Kuwaki, Tomoyuki, Ootsuka, Youichirou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804267/
https://www.ncbi.nlm.nih.gov/pubmed/35128515
http://dx.doi.org/10.1016/j.ibneur.2022.01.002
_version_ 1784643038719508480
author Miyata, Kohei
Ikoma, Yoko
Murata, Koshi
Kusumoto-Yoshida, Ikue
Kobayashi, Kenta
Kuwaki, Tomoyuki
Ootsuka, Youichirou
author_facet Miyata, Kohei
Ikoma, Yoko
Murata, Koshi
Kusumoto-Yoshida, Ikue
Kobayashi, Kenta
Kuwaki, Tomoyuki
Ootsuka, Youichirou
author_sort Miyata, Kohei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8804267
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-88042672022-02-04 Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate Miyata, Kohei Ikoma, Yoko Murata, Koshi Kusumoto-Yoshida, Ikue Kobayashi, Kenta Kuwaki, Tomoyuki Ootsuka, Youichirou IBRO Neurosci Rep Research Paper 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. Elsevier 2022-01-19 /pmc/articles/PMC8804267/ /pubmed/35128515 http://dx.doi.org/10.1016/j.ibneur.2022.01.002 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Miyata, Kohei
Ikoma, Yoko
Murata, Koshi
Kusumoto-Yoshida, Ikue
Kobayashi, Kenta
Kuwaki, Tomoyuki
Ootsuka, Youichirou
Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title_full Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title_fullStr Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title_full_unstemmed Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title_short Multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
title_sort multifaceted roles of orexin neurons in mediating methamphetamine-induced changes in body temperature and heart rate
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804267/
https://www.ncbi.nlm.nih.gov/pubmed/35128515
http://dx.doi.org/10.1016/j.ibneur.2022.01.002
work_keys_str_mv AT miyatakohei multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT ikomayoko multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT muratakoshi multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT kusumotoyoshidaikue multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT kobayashikenta multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT kuwakitomoyuki multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate
AT ootsukayouichirou multifacetedrolesoforexinneuronsinmediatingmethamphetamineinducedchangesinbodytemperatureandheartrate