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

Katalin Eszter Ibos,Zsolt Bagosi,Gábor Tóth,Éva Bodnár,Krisztina Csabafi,Gyula Szabó,Zsolt Bozsó

doi:10.3390/biomedicines9020112

Katalin Eszter Ibos, Zsolt Bagosi + Show 5 more

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https://doi.org/10.3390/biomedicines9020112

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Journal: Biomedicines	Publication Date: Jan 25, 2021
Citations: 17	License type: CC BY 4.0

Affiliation: University of Szeged

Abstract

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.

Highlights

The KISS1 gene was discovered as a novel metastasis-suppressor in human melanoma cells in 1996 in Hershey, named after the famous chocolate of the city, Hershey’s Kisses [1]
The 0.1 μg dose of Kp-8 significantly reduced the percentage of entries into the open arms of the plus maze (Figure 1a, F (2, 20) = 9.196, p = 0.0007), as well as the percentage of time spent in the open arms of the maze (Figure 1b, F (2, 20) = 4.431, p = 0.0202)
Short kisspeptinconditions analogs are promising candidates in the treatment of infertility and other gynecological. Kisspeptins exert their effect on the reproductive axis

Summary

Introduction

KISS1 encodes a 145-amino-acid propeptide, from which kisspeptin-54 (Kp-54) is cleaved. The proteolytical cleavage of this 54-amino-acid peptide results in shorter biologically active products, designated kisspeptin-14 (Kp-14), kisspeptin-13 (Kp-13) and kisspeptin-10 (Kp-10) [2]. Mammalian kisspeptins belong to the family of RF-amide peptides, as they carry the characteristic, conserved carboxyl-terminal Arg–Phe–NH2 sequence [3]. The canonical receptor of kisspeptins is a G protein-coupled receptor, Gpr, that is fully activated by all biologically active products of the Kiss gene [4]. Gpr was initially described in 1999 as an orphan receptor similar to galanin receptors [5], after being deorphanized in 2001, it was designated kisspeptin-1 receptor (Kiss1r) [6]

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