Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), comp...

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Main Authors: Katalin Eszter Ibos, Éva Bodnár, Zsolt Bagosi, Zsolt Bozsó, Gábor Tóth, Gyula Szabó, Krisztina Csabafi
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/2/112
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author Katalin Eszter Ibos
Éva Bodnár
Zsolt Bagosi
Zsolt Bozsó
Gábor Tóth
Gyula Szabó
Krisztina Csabafi
author_facet Katalin Eszter Ibos
Éva Bodnár
Zsolt Bagosi
Zsolt Bozsó
Gábor Tóth
Gyula Szabó
Krisztina Csabafi
author_sort Katalin Eszter Ibos
collection DOAJ
description Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.
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spelling doaj.art-f230508598324203b16bc6cfb974cbad2023-12-03T14:32:19ZengMDPI AGBiomedicines2227-90592021-01-019211210.3390/biomedicines9020112Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in RatsKatalin Eszter Ibos0Éva Bodnár1Zsolt Bagosi2Zsolt Bozsó3Gábor Tóth4Gyula Szabó5Krisztina Csabafi6Department of Pathophysiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryDepartment of Pathophysiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryDepartment of Pathophysiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryOffice of International Affairs, Budapest Campus, McDaniel College, H-1071 Budapest, HungaryDepartment of Pathophysiology, Faculty of Medicine, University of Szeged, H-6720 Szeged, HungaryKisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.https://www.mdpi.com/2227-9059/9/2/112kisspeptinanxietylocomotionKiss1 receptorHPA axisHPG axis
spellingShingle Katalin Eszter Ibos
Éva Bodnár
Zsolt Bagosi
Zsolt Bozsó
Gábor Tóth
Gyula Szabó
Krisztina Csabafi
Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
Biomedicines
kisspeptin
anxiety
locomotion
Kiss1 receptor
HPA axis
HPG axis
title Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
title_full Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
title_fullStr Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
title_full_unstemmed Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
title_short Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats
title_sort kisspeptin 8 induces anxiety like behavior and hypolocomotion by activating the hpa axis and increasing gaba release in the nucleus accumbens in rats
topic kisspeptin
anxiety
locomotion
Kiss1 receptor
HPA axis
HPG axis
url https://www.mdpi.com/2227-9059/9/2/112
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