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.
