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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 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.

Authors+Show Affiliations

Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. Department of Biomolecular Pharmacology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31618533

Citation

Yonemochi, Naomi, et al. "GABAergic Function in the Lateral Hypothalamus Regulates Feeding Behavior: Possible Mediation Via Orexin." Neuropsychopharmacology Reports, 2019.
Yonemochi N, Ardianto C, Ueda D, et al. GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin. Neuropsychopharmacol Rep. 2019.
Yonemochi, N., Ardianto, C., Ueda, D., Kamei, J., & Ikeda, H. (2019). GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin. Neuropsychopharmacology Reports, doi:10.1002/npr2.12080.
Yonemochi N, et al. GABAergic Function in the Lateral Hypothalamus Regulates Feeding Behavior: Possible Mediation Via Orexin. Neuropsychopharmacol Rep. 2019 Oct 16; PubMed PMID: 31618533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin. AU - Yonemochi,Naomi, AU - Ardianto,Chrismawan, AU - Ueda,Daiki, AU - Kamei,Junzo, AU - Ikeda,Hiroko, Y1 - 2019/10/16/ PY - 2019/07/17/received PY - 2019/09/22/revised PY - 2019/09/24/accepted PY - 2019/10/17/entrez PY - 2019/10/17/pubmed PY - 2019/10/17/medline KW - GABAA receptors KW - food intake KW - hypothalamus KW - mice KW - neuropeptides JF - Neuropsychopharmacology reports JO - Neuropsychopharmacol Rep N2 - 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. SN - 2574-173X UR - https://www.unboundmedicine.com/medline/citation/31618533/GABAergic_function_in_the_lateral_hypothalamus_regulates_feeding_behavior:_Possible_mediation_via_orexin L2 - https://doi.org/10.1002/npr2.12080 DB - PRIME DP - Unbound Medicine ER -