The action of kisspeptin-13 on passive avoidance learning in mice. Involvement of transmitters

Abstract

Kisspeptins are G protein-coupled receptor ligands originally identified as human metastasis suppressor gene products that have the ability to suppress melanoma and breast cancer metastasis and recently found to play an important role in initiating the secretion of gonadotropin-releasing hormone at puberty. Kisspeptin-13 is an endogenous isoform that consists of 13 amino acids. The action of kisspeptin in the regulation of gonadal function has been widely studied, but little is known as concerns its function in limbic brain structures. In the brain, the gene is transcribed within the hippocampal dentate gyrus. This paper reports on a study the effects of kisspeptin-13 on passive avoidance learning and the involvement of the adrenergic, serotonergic, cholinergic, dopaminergic and GABA-A-ergic, opiate receptors and nitric oxide in its action in mice. Mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, an α2-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a nonselective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist, atropine, D2, D3, D4 dopamine receptor antagonist, haloperidol, a γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline, naloxone, a nonselective opioid receptor antagonist and nitro-l-arginine, a nitric oxide synthase inhibitor. Kisspeptin-13 facilitated learning and memory consolidation in a passive avoidance paradigm. Phenoxybenzamine, yohimbine, propranolol, methysergide, cyproheptadine, atropine, bicuculline and nitro-l-arginine prevented the action of kisspeptin-13 on passive avoidance learning, but haloperidol and naloxone did not block the effects of kisspeptin-13. The results demonstrated that the action of kisspeptin-13 on the facilitation of passive avoidance learning and memory consolidation is mediated, at least in part, through interactions of the α2-adrenergic, beta-adrenergic, 5-HT2 serotonergic, muscarinic cholinergic and GABA-A-ergic receptor systems and nitric oxide.

The Role of Neurotransmitters in Protection against Amyloid-β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons

“…The KP peptide facilitates passive avoidance learning and memory consolidation in vivo , which can be inhibited by muscarinic but not nicotinic cholinergic antagonists [17]. The effects of muscarinic and nicotinic cholinergic antagonists on KiSS-1 overexpression neuroprotection against A β were therefore tested.…”

“…However, in vivo actions on the opioid system [12, 13], oxytocin/vasopressin systems [4, 14, 15], neurotransmitter systems [16, 17], activation of endogenous antioxidants [18], activation of nitric oxide [17], and possible activation of prostaglandin synthesis [19] have not been tested with GPR-54 or NPFF receptor antagonists.…”

Habenular kisspeptin modulates fear in the zebrafish

“…This indicates that Kiss1 does not return various parameters to controls but far exceeds them. This raises the possibility that the kisspeptin "reversal" of AS effects, as well as anxiolytic effect, could be partly occurring through an interaction of other neurotransmitters, such as adrenergic and cholinergic neurons (33,35).…”

“…As the mammalian brain functions advanced, along with the development of additional brain structures such as the cortex and the hippocampus, during evolution, the classical fear pathways have also evolved to prepare and respond to aversive stimuli that are potentially life threatening. Interestingly, a very recent report demonstrated the effects of kisspeptin-13 on passive avoidance learning in mice (35). Because the hypothalamus and the amygdala express kisspeptin and Kiss-R (2, 4, 43), it is possible that kisspeptin-Kiss-R signaling could be involved in the contextualization of fear in mammals (44).…”

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

“…The peptide takes part in cardiovascular [136] and metabolic [17] functions, pregnancy [11] and cognitive processes [3,215]. Clearly, the control of the aforementioned processes necessitates integration with gonadal activities.…”