Reviews on Clinical Pharmacology and Drug TherapyReviews on Clinical Pharmacology and Drug Therapy1683-41002542-1875Eco-Vector7061710.17816/RCF19147-53Research ArticleConditioned place preference of kisspeptin-10TissenIlia Yu.<p>PhD, Cand. Sci. (Biol.), Senior Researcher</p>iljatis@mail.ruhttps://orcid.org/0000-0002-8710-9580ChepikPolina A.<p>Post-graduate Fellow</p>aalebedev-iem@rambler.ruLebedevAndrei A.<p>Dr. Biol. Sci. (Pharmacology)</p>aalebedev-iem@rambler.ruhttps://orcid.org/0000-0003-0297-0425MagarramovaLeila A.<p>Post-graduate</p>alexandrablazhenko@gmail.comBychkovEugenii R.<p>PhD (Pathophysiology), Cand. Sci. (Med.)</p>bychkov@mail.ruhttps://orcid.org/0000-0002-8911-6805ShabanovPetr D.<p>Dr. Med. Sci. (Pharmacology), Professor</p>pdshabanov@mail.ruhttps://orcid.org/0000-0003-1464-1127Institute of Experimental Medicine1503202119147531405202114052021Copyright © 2021, Tissen I.Y., Chepik P.A., Lebedev A.A., Magarramova L.A., Bychkov E.R., Shabanov P.D.2021<p><em>INTRODUCTION:</em> Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS.</p>
<p>The <em>aim</em> of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration.</p>
<p><em>METHODS:</em> Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats.</p>
<p><em>RESULTS:</em> When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; <em>p</em> 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (<em>p</em> 0.05), and the number of sniffings was 2-fold increased too (<em>p</em> 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL.</p>
<p><em>CONCLUSION:</em> Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.</p>kisspeptin-10sexual behaviorconditioned place preferenceemotional behaviorкисспептин-10половое поведениеусловная реакция предпочтения местаэмоциональное поведение[Arai AC. The role of kisspeptin and GPR54 in the hippocampus. Peptides. 2009;30(1):16–25. DOI: 10.1016/j.peptides.2008.07.023][Baik JH. Dopamine signaling in reward-related behaviors. Front Neural Circuits. 2013;7:152. DOI: 10.3389/fncir.2013.00152][De Bond JA, Smith JT. Kisspeptin and energy balance in reproduction. Reproduction. 2014;147(3): R53–R63. DOI: 10.1530/REP-13-0509][Dudek M, Ziarniak K, Sliwowska JH. Kisspeptin and metabolism: The brain and beyond. Front Endocrinol. 2018;(9):145. DOI: 10.3389/fendo.2018.00145][Edouard GA, Mills KT, Comninos AN. Kisspeptin as a behavioral hormone. Semin Reprod Med. 2019;37(2):56–63. DOI: 10.1055/s-0039-3400239][Gibula-Tarlowska E, Grochecki P, Silberring J, Kotlinska JH. The kisspeptin derivative kissorphin reduces the acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in rats. Alcohol. 2019;81:11–19. DOI: 10.1016/j.alcohol.2019.04.001][Kelley AE. Memory and addiction: shared neural circuitry and molecular mechanisms // Neuron. 2004;44(1):161–179. DOI: 10.1016/j.neuron.2004.09.016][Liu X, Herbison A. Kisspeptin regulation of neuronal activity throughout the central nervous system. Endocrinol Metab (Seoul). 2016;31(2):193–205. DOI: 10.3803/EnM.2016.31.2.193][Merrer JL, Becker JA, Befort K, Kieffer BL. Reward processing by the opioid system in the brain. Physiol Rev. 2009;89(4): 1379–1412. DOI: 10.1152/physrev.00005.2009][Oishi S, Misu R, Tomita K, et al. Activation of neuropeptide FF receptors by kisspeptin receptor ligands 2011. ACS Med Chem Lett. 2011;2(1):53–57. DOI: 10.1021/ml1002053][Mills EG, Dhillo WS, Comninos AN. Kisspeptin and the control of emotions, mood and reproductive behavior. J Endocrinol. 2018;239(1): R1–R12. DOI: 10.1530/JOE-18-0269][Rønnekleiv OK, Kelly MJ. Kisspeptin excitation of GnRH neurons. Adv Exp Med Biol. 2013;784:113–131. DOI: 10.1007/978-1-4614-6199-9_6][Shabanov PD, Lebedev AA. Involvement of GABA and dopaminergic mechanisms of the bed nucleus of the stria terminalis in the reinforcing effects of psychotropic substances mediated via the lateral hypothalamus. Neurosci Behav Physiol. 2013;43(4):485–491][Tena-Sempere M. Roles of kisspeptins in the control of hypothalamic-gonadotropic function: focus on sexual differentiation and puberty onset. Endocr Dev. 2010;17:52–62. DOI: 10.1159/000262528][Tchenio A, Valentinova K, Mameli M. Can the lateral habenula crack the serotonin code? Front Synaptic Neurosci. 2016;8:34. DOI: 10.3389/fnsyn.2016.00034][Tissen I, Magarramova L, Kraskova A, et al. P. 578 Kisspeptin steroid-independently regulated sexual motivation in male rats. Eur Neuropsychopharmacology. 2019;29 Suppl 6: S404–S405. DOI: 10.1016/j.euroneuro.2019.09.577][Tng EL. Kisspeptin signalling and its roles in humans. Singapore Med J. 2015;56(12):649–656. DOI: 10.11622/smedj.2015183][Zhao Y, Singh C, Prober DA, Wayne NL. Morphological and physiological interactions between GnRH3 and hypocretin/orexin neuronal systems in zebrafish (Danio rerio). Endocrinology. 2016;157(10):4012-4020. DOI: 10.1210/en.2016-1381]