The role of 5-HT2A and 5-HT2C subtypes of serotonergic receptors in the control of sexual behavior and plasma testosterone regulation was studied in male CBA mice exposed to a sexually receptive female separated by a transparent partition. Introduction of the receptive female induced sexual motivation and arousal in males, as evidenced by a prolonged time spent at the partition, unsuccessful attempts to step across it and a significant increase in plasma testosterone levels. Administration of 5-HT2A receptor antagonists ketanserin (1.0 and 2.0 mg/kg i.p.) or cyproheptadine (1.0 and 2.0 mg/kg i.p.) diminished the behavioral components and prevented the hormonal components of male sexual arousal. Administration of the selective 5-HT2C antagonist RS 102221 (1.0 and 2.0 mg/kg) considerably increased the time spent by males at the partition (p < 0.001) and, at the dose of 2.0 mg/kg, increased plasma testosterone levels (p < 0.01). Administration of ritanserin – a nonselective 5-HT2A/2C antagonist and, to a smaller degree, 5-HT2B antagonist – at doses of 0.1 and 0.5 mg/kg did not significantly influence male behavior and the activating effect of the presence of a female on the hypothalamo-pituitary-testicular system, although it increased resting testosterone levels (p < 0.05). The present findings suggest that 5-HT2A/5-HT2C receptors may be involved in the neural control of male sexual motivation and arousal, presumably by exerting reciprocal facilitative (5-HT2A) or suppressive (5-HT2C) influences.

1.
Naumenko EV, Shishkina GT: Role of serotonin in feedback control of hypothalamic-pituitary-testicular complex in male rats. Neuroendocrinology 1978;26:359–366.
2.
Armario A, Marti O, Gavalda A, Lopez-Calderon A: Evidence for the involvement of serotonin in acute stress-induced release of luteinizing hormone in the male rat. Brain Res Bull 1993;31:29–31.
3.
Popova NK, Naumenko EV, Kolpakov VG: Serotonin and Behavior (in Russian). Novosibirsk, Nauka, 1978.
4.
Olivier B, van Oorschot R, Waldinger MD: Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol 1998;13(suppl 6):S9–S14.
5.
Bancroft J: Central inhibition of sexual response in the male: A theoretical perspective. Neurosci Biobehav Rev 1999;23:763–784.
6.
Shishkina GT, Dygalo NN: Role of the serotoninergic system in the acceleration of sexual maturation in wild Norway rats selected for reduced aggressiveness toward humans. Comp Biochem Physiol C Toxicol Pharmacol 2000;125:45–51.
7.
Agmo A: Sexual motivation – an inquiry into events determining the occurrence of sexual behavior. Behav Brain Res 1999;105:129–150.
8.
Beach FA: Behavioral neuroendocrinology and the study of reproduction. Biol Reprod 1974;10:2–18.
9.
Popova NK, Amstislavskaya TG, Kucheryavy SA: Sexual motivation in male mice induced by female exposure (in Russian). Zh Vyssh Nerv Deiat Im I P Pavlova 1998;48:84–90.
10.
Naumenko EV, Osadchuk AV, Serova LI: Genetic and neuroendocrine mechanisms underlying the control of hypothalamic-hypophysial-testicular complex during sexual arousal. Sov Sci Rev F Physiol Gen Biol 1992;5:1–38.
11.
Vega Matuszcyk J, Larsson K, Eriksson E: The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol Biochem Behav 1998;60:527–532.
12.
Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PA: International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994;46:157–200.
13.
Barnes NM, Sharp T: A review of central 5-HT receptors and their function. Neuropharmacology 1999;39:1083–1152.
14.
Popova NK; Amstislavskaya TG: Involvement of the 5-HT1A and 5-HT1B serotonergic receptor subtypes in sexual arousal in male mice. Psychoneuroendocrinology, in press.
15.
Julius D, Huang KN, Livelli TJ, Axel R, Jessell TM: The 5-HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors. Proc Natl Acad Sci USA 1990;87:928–932.
16.
Hoyer D, Martin GR: Classification and nomenclature of 5-HT receptors: A comment on current issues. Behav Brain Res 1996;73:263–268.
17.
Ronken E, Olivier B: The 5-HT-type receptor family; in Olivier B, van Wijngarden I, Soudijn W (eds): Serotonin Receptors and Their Ligands. Amsterdam, Elsevier, 1997, pp 199–214.
18.
Foreman MM, Hall JL, Love RL: The role of the 5-HT2 receptor in the regulation of sexual performance of male rats. Life Sci 1989;45:1263–1270.
19.
Klint T, Dahlgren IL, Larsson K: The selective 5-HT2 receptor antagonist amperozide attenuates 1-(2,5-dimetoxy-4-iodophenyl)-2-aminopropane-induced inhibition of male rat sexual behavior. Eur J Pharmacol 1992;212:241–246.
20.
Klint T, Larsson K: Clozapine acts as a 5-HT2 antagonist by attenuating DOI-induced inhibition of male rat sexual behaviour. Psychopharmacology (Berl) 1995;119:291–294.
21.
Naumenko EV, Amstislavskaya TG, Osadchuk AV: The role of adrenoceptors in the activation of the hypothalamic-pituitary-testicular complex of mice induced by the presence of a female. Exp Clin Endocrinol 1991;97:1–12.
22.
Griebel G: 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: More than 30 years of research. Pharmacol Ther 1995;65:319–395.
23.
Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: A novel high affinity and selective 5HT2C receptor antagonist. Neuropharmacology 1997;36:621–629.
24.
Baxter G, Kennett G, Blaney F, Blackburn T: 5-HT2 receptor subtypes: A family re-united? Trends Pharmacol Sci 1995;16:105–110.
25.
Amstislavsky SY, Amstislavskaya TG, Eroschenko VP: Methoxychlor given in the periimplantation period blocks sexual arousal in male mice. Reprod Toxicol 1999;13:405–411.
26.
Novikov SN: Pheromones and Reproduction in Mammals: Physiological Aspects (in Russian). Leningrad, Nauka, 1988.
27.
Morozov VI, Tchaikowsky VS, Pryatkin SA, Rogozkin VA, Savchenko ON, Shaliapina VG, Zorina AD, Lushchitskaya IM, Saltykova IA, Mishin VI, Timofeeva LA, Stepanov GS: Radioimmunoassay of steroids. Scientific and practical aspects. Physiologichesky J 1988;8:1049–1072.
28.
Leysen JE, Niemegeers CJE, van Nueten JM, Laduron PM: [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution, and functional role. Mol Pharmacol 1982;21:301–314.
29.
Leysen JE: Use of 5-HT receptor agonists and antagonists for the characterization of their respective receptor sites. Neuromethods 1989;12:299–350.
30.
Meyerson BJ: Drugs and sexual motivation in the female rat; in Sandler M, Gessa G (eds): Sexual Behavior: Pharmacology and Biochemistry. New York, Raven, 1975, pp 21–32.
31.
Maruniak JA, Bronson FH: Gonadotropic responses of male mice to female urine. Endocrinology 1976;99:963–969.
32.
Pazos A, Cortes R, Palacios J: Quantitative autoradiographic mapping of serotonin receptors in the rat brain. 2. Serotonin-2 receptors. Brain Res 1985;346:231–249.
33.
Zifa E, Fillion G: 5-Hydroxytryptamine receptors. Pharmacol Rev 1992;44:401–458.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.