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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2021-01-01
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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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