GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin

Abstract Aim The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feed...

Full description

Bibliographic Details
Main Authors: Naomi Yonemochi, Chrismawan Ardianto, Daiki Ueda, Junzo Kamei, Hiroko Ikeda
Format: Article
Language:English
Published: Wiley 2019-12-01
Series:Neuropsychopharmacology Reports
Subjects:
Online Access:https://doi.org/10.1002/npr2.12080
_version_ 1811185666042626048
author Naomi Yonemochi
Chrismawan Ardianto
Daiki Ueda
Junzo Kamei
Hiroko Ikeda
author_facet Naomi Yonemochi
Chrismawan Ardianto
Daiki Ueda
Junzo Kamei
Hiroko Ikeda
author_sort Naomi Yonemochi
collection DOAJ
description Abstract Aim The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feeding behavior. Methods GABA levels in the LH were measured by in vivo microdialysis. Food intake after drug injection into the LH was measured every 1 hour for 4 hours. The mRNA levels were measured using RT‐PCR. Results Food intake significantly increased GABA levels in the LH, suggesting that food intake stimulates GABAergic function in the LH. Injection of the GABAA receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABAA receptor antagonist bicuculline into the LH did not significantly affect food intake. The inhibitory effect of muscimol injected into the LH was blocked by co‐administration of bicuculline. These results indicate that the stimulation of GABAA receptors in the LH inhibits food intake. We next examined whether the stimulation of GABAA receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus. Conclusion These results indicate that food intake activates GABAergic function in the LH, which terminates feeding behavior by stimulating GABAA receptors. Moreover, it is suggested that the stimulation of GABAA receptors in the LH reduces food intake through inhibition of orexin neurons.
first_indexed 2024-04-11T13:33:04Z
format Article
id doaj.art-3c37aaa2b70c4190b44ae2165a3668e4
institution Directory Open Access Journal
issn 2574-173X
language English
last_indexed 2024-04-11T13:33:04Z
publishDate 2019-12-01
publisher Wiley
record_format Article
series Neuropsychopharmacology Reports
spelling doaj.art-3c37aaa2b70c4190b44ae2165a3668e42022-12-22T04:21:41ZengWileyNeuropsychopharmacology Reports2574-173X2019-12-0139428929610.1002/npr2.12080GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexinNaomi Yonemochi0Chrismawan Ardianto1Daiki Ueda2Junzo Kamei3Hiroko Ikeda4Department of Pathophysiology and Therapeutics Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo JapanDepartment of Pathophysiology and Therapeutics Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo JapanDepartment of Pathophysiology and Therapeutics Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo JapanDepartment of Pathophysiology and Therapeutics Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo JapanDepartment of Pathophysiology and Therapeutics Hoshi University School of Pharmacy and Pharmaceutical Sciences Tokyo JapanAbstract Aim The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feeding behavior. Methods GABA levels in the LH were measured by in vivo microdialysis. Food intake after drug injection into the LH was measured every 1 hour for 4 hours. The mRNA levels were measured using RT‐PCR. Results Food intake significantly increased GABA levels in the LH, suggesting that food intake stimulates GABAergic function in the LH. Injection of the GABAA receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABAA receptor antagonist bicuculline into the LH did not significantly affect food intake. The inhibitory effect of muscimol injected into the LH was blocked by co‐administration of bicuculline. These results indicate that the stimulation of GABAA receptors in the LH inhibits food intake. We next examined whether the stimulation of GABAA receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus. Conclusion These results indicate that food intake activates GABAergic function in the LH, which terminates feeding behavior by stimulating GABAA receptors. Moreover, it is suggested that the stimulation of GABAA receptors in the LH reduces food intake through inhibition of orexin neurons.https://doi.org/10.1002/npr2.12080food intakeGABAA receptorshypothalamusmiceneuropeptides
spellingShingle Naomi Yonemochi
Chrismawan Ardianto
Daiki Ueda
Junzo Kamei
Hiroko Ikeda
GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
Neuropsychopharmacology Reports
food intake
GABAA receptors
hypothalamus
mice
neuropeptides
title GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
title_full GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
title_fullStr GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
title_full_unstemmed GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
title_short GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin
title_sort gabaergic function in the lateral hypothalamus regulates feeding behavior possible mediation via orexin
topic food intake
GABAA receptors
hypothalamus
mice
neuropeptides
url https://doi.org/10.1002/npr2.12080
work_keys_str_mv AT naomiyonemochi gabaergicfunctioninthelateralhypothalamusregulatesfeedingbehaviorpossiblemediationviaorexin
AT chrismawanardianto gabaergicfunctioninthelateralhypothalamusregulatesfeedingbehaviorpossiblemediationviaorexin
AT daikiueda gabaergicfunctioninthelateralhypothalamusregulatesfeedingbehaviorpossiblemediationviaorexin
AT junzokamei gabaergicfunctioninthelateralhypothalamusregulatesfeedingbehaviorpossiblemediationviaorexin
AT hirokoikeda gabaergicfunctioninthelateralhypothalamusregulatesfeedingbehaviorpossiblemediationviaorexin