Neurotransmissions of Antidepressant-like Effects of Kisspeptin-13

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 which have recently been found to play an important role in initiating the secretion of gonadotropin-releasing hormone at puberty. In the brain, the gene is transcribed within the hippocampal dentate gyrus. Kisspeptin-13, one of the endogenous isoforms, consists of 13 amino acids. In this work, antidepressant-like effects of kisspeptin-13 were studied and the potential involvement of the adrenergic, serotonergic, cholinergic, dopaminergic and gabaergic receptors in its antidepressant-like effects was investigated in a modified forced swimming test (FST) in mice. The mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, an α(1)/α(2β)-adrenergic receptor antagonist, prazosin, an α(2)-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist, methysergide, a nonselective 5-HT(2) serotonergic receptor antagonist, cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist, atropine, a D(2),D(3),D(4) dopamine receptor antagonist, haloperidol, or a γ-aminobutyric acid subunit A receptor antagonist, bicuculline. The FST revealed that kisspeptin-13 reversed the immobility, climbing and swimming times, suggesting antidepressant-like effects. Phenoxybenzamine, yohimbine and cyproheptadine prevented the effects of kisspeptin-13 on the immobility, climbing and swimming times, whereas prazosin, propranolol, methysergide, atropine, haloperidol and bicuculline did not modify the effects of kisspeptin-13. The results demonstrated that the antidepressant-like effects of kisspeptin-13 in a modified mouse FST are mediated, at least in part, by an interaction of the α(2)-adrenergic and 5-HT(2) serotonergic receptors.