Sexual motivation and performance in sexual naïve and experienced rats treated with ivermectin: an ultrasonic vocalization study

Authors

  • Paula da Silva Rodrigues Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-6870-0930
  • Ana Claudia Silva Sampaio Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-2298-2629
  • Éricka Patrícia da Silva Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-4573-2921
  • Ivana Barbosa Suffredini Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-5237-101X
  • Eduardo Fernandes Bondan Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-3887-0023
  • Maria Martha Bernardi Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-6860-9416
  • Thiago Berti Kirsten Universidade Paulista, Programa de Pós-graduação Patologia Ambiental e Experimental, Laboratório de Psiconeuroimunologia, São Paulo – SP, Brazil https://orcid.org/0000-0002-4032-4355

DOI:

https://doi.org/10.11606/issn.1678-4456.bjvras.2023.198441

Keywords:

Sexual behavior, Ultrasonic vocalizations, Latency to the first mount, Motivation

Abstract

In mammals, ivermectin acts as a GABAA receptor agonist and stimulates GABA release. Previous studies showed that ivermectin (IVM) reduces sexual performance, impairing the latency to the first mount and intromission. These parameters are usually considered motivational parameters of sexual behavior. However, IVM increases GABAergic activity leading to motor incoordination. Thus, it is reasonable to propose that IVM affects sexual performance via motor incoordination pathways. The present study analyzed ultrasonic vocalization in rats to verify whether IVM impairs sexual behavior via motivational mechanisms or motor impairment. Because sexual experience attenuates the impairment of motor performance, rats with sexual experience were also studied. Sexually naive and experienced rats were administered a therapeutic IVM dose and saline. The rats were exposed to receptive females, and the latency to the first mount was evaluated, followed by the 50-kHz USV test. IVM treatment in naïve rats increased the latency to first to mount relative to Saline naïve rats, while no differences were observed between saline and experienced rats. In naïve-IVM rats, a reduced frequency and total calls and increased mean time of calls occur relative to SAL-naïve rats. Experienced IVM rats did not show differences in the frequency, mean, and maximal calls close to Saline experienced rats. However, an increase in the total calls and the dominant frequency of calls were observed in IVM-experienced rats compared to Saline experienced rats. A negative and positive correlation occurred between the latency to the first mount and USVs in groups with and without ivermectin exposure. Hence, we propose that ivermectin increased the sexual motivation of rats exposed to a female in estrous based in USVs despite an increased latency to the first mount that occurred. The increased latency to the first mount resulted from motor incoordination, as previously observed and proposed by our group.

Downloads

Download data is not yet available.

References

Agmo A, Paredes R, Fernández H. Differential effects of GABA transaminase inhibitors on sexual behavior, locomotor activity, and motor execution in the male rat. Pharmacol Biochem Behav. 1987;28(1):47-52. http://doi.org/10.1016/0091-3057(87)90010-4. PMid:3116562.

Agmo A, Paredes R. GABAergic drugs and sexual behaviour in the male rat. Eur J Pharmacol. 1985;112(3):371-8. http://doi.org/10.1016/0014-2999(85)90783-6. PMid:2990971.

Agmo A. Male rat sexual behavior. Brain Res Brain Res Protoc. 1997;1(2):203-9. http://doi.org/10.1016/S1385-299X(96)00036-0. PMid:9385085.

Albers-Schoenberg G, Arison BH, Chabala JC, Douglas AW, Eskola P, Fisher MH, Lusi A, Mrozik H, Smith JL, Tolman RL. Avermectins. Structure determination. J Am Chem Soc. 1981;103(14):4216-21. http://doi.org/10.1021/ja00404a040.

Barfield RJ, Auerbach P, Geyer L, Mcintosh T. Ultrasonic vocalizations in rat sexual behavior. Am Zool. 1979;19(2):469-80. http://doi.org/10.1093/icb/19.2.469.

Bernardi MM, Kirsten TB, Spinosa HS, Manzano H. Ivermectin impairs sexual behavior in sexually naïve, but not sexually experienced male rats. Res Vet Sci. 2011;91(1):77-81. http://doi.org/10.1016/j.rvsc.2010.07.026. PMid:20800249.

Bernardi MM, Kirsten TB, Teodorov E, Baso ACZ, Prosdocimi FC, Felicio LF. Maternal exposure to picrotoxin modifies the response of the GABAA receptor during sexual behavior of adult male rat offspring. Behav Pharmacol. 2012;23(7):703-9. http://doi.org/10.1097/FBP.0b013e3283586072. PMid:22914075.

Bialy M, Rydz M, Kaczmarek L. Precontact 50-kHz vocalizations in male rats during acquisition of sexual experience. Behav Neurosci. 2000;114(5):983-90. http://doi.org/10.1037/0735-7044.114.5.983. PMid:11085613.

Bialy M, Podobinska M, Barski J, BogackiRychlik W, SajdelSulkowska E. Distinct classes of low frequency ultrasonic vocalizations in rats during sexual interactions relate to different emotional states. Acta Neurobiol Exp (Warsz). 2019;79(1):1-12. http://doi.org/10.21307/ane-2019-001.

Bogacki-Rychlik W, Rolf M, Bialy M. Anticipatory 50-kHz precontact ultrasonic vocalizations and sexual motivation: characteristic pattern of ultrasound subtypes in an individual analyzed profile. Front Behav Neurosci. 2021;15:722456. http://doi.org/10.3389/fnbeh.2021.722456. PMid:34489656.

Brudzynski SM. Biological functions of rat ultrasonic vocalizations, arousal mechanisms, and call initiation. Brain Sci. 2021;11(5):605. http://doi.org/10.3390/brainsci11050605. PMid:34065107.

Burgdorf J, Kroes RA, Moskal JR, Pfaus JG, Brudzynski SM, Panksepp J. Ultrasonic vocalizations of rats (Rattus norvegicus) during mating, play, and aggression: behavioral concomitants, relationship to reward, and self-administration of playback. J Comp Psychol. 2008;122(4):357-67. http://doi.org/10.1037/a0012889. PMid:19014259.

Burgdorf J, Panksepp J, Brudzynski SM, Kroes R, Moskal JR. Breeding for 50-kHz positive affective vocalization in rats. Behav Genet. 2005;35(1):67-72. http://doi.org/10.1007/s10519-004-0856-5.

Campbell WC. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Curr Pharm Biotechnol. 2012;13(6):853-65. http://doi.org/10.2174/138920112800399095. PMid:22039784.

Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent. Science. 1983;221(4613):823-8. http://doi.org/10.1126/science.6308762. PMid:6308762.

Cordeiro F, Gonçalves Júnior V, Moreira N, Slobodticov JI, Galvão NA, Spinosa HS, Bonamin LV, Bondan EF, Ciscato CHP, Barbosa CM, Bernardi MM. Ivermectin acute administration impaired the spermatogenesis and spermiogenesis of adult rats. Res Vet Sci. 2018;117:178-86. PMid:29288959.

Dawson GR, Wafford KA, Smith A, Marshall GR, Bayley PJ, Schaeffer JM, Meinke PT, McKernan RM. Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the γ-aminobutyric acid(A) receptor. J Pharmacol Exp Ther. 2000;295(3):1051-60. PMid:11082440.

Elgart GW, Meinking TL. Ivermectin. Dermatol Clin. 2003;21(2):277-82. http://doi.org/10.1016/S0733-8635(02)00095-5. PMid:12757250.

Eng J. Sample size estimation: how many individuals should be studied? Radiology. 2003;227(2):309-13. http://doi.org/10.1148/radiol.2272012051. PMid:12732691.

Ferri R, Silva AFST, Cabral D, Moreira N, Spinosa HS, Bernardi MM. Doramectin reduces sexual behavior and penile erection in male rats. Neurotoxicol Teratol. 2013;39:63-8. http://doi.org/10.1016/j.ntt.2013.07.006. PMid:23899514.

Galef BG. Necessary and sufficient conditions for communication of diet preferences by Norway rats. Anim Learn Behav. 1990;18(4):347-51. http://doi.org/10.3758/BF03205316.

Harding SMS, McGinnis MMY. Effects of testosterone in the VMN on copulation, partner preference, and vocalizations in male rats. Horm Behav. 2003;43(2):327-35. http://doi.org/10.1016/S0018-506X(02)00049-1. PMid:12694643.

Himmler BT, Kisko TM, Euston DR, Kolb B, Pellis SM. Are 50-kHz calls used as play signals in the playful interactions of rats? I. Evidence from the timing and context of their use. Behav Processes. 2014;106:60-6. http://doi.org/10.1016/j.beproc.2014.04.014.

Hotson IK. The avermectins: a new family of antiparasitic agents. J S Afr Vet Assoc. 1982;53(2):87-90. PMid:6750121.

Kisko TM, Wöhr M, Pellis VC, Pellis SM. From play to aggression: high-frequency 50-kHz ultrasonic vocalizations as play and appeasement signals in rats. Curr Top Behav Neurosci. 2017;30:91-108. http://doi.org/10.1007/7854_2015_432.

Lee S-E, Lee Y, Lee GH. The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain. Arch Pharm Res. 2019;42(12):1031-9. http://doi.org/10.1007/s12272-019-01196-z. PMid:31786745.

López HH, Olster DH, Ettenberg A. Sexual motivation in the male rat: the role of primary incentives and copulatory experience. Horm Behav. 1999;36(2):176-85. http://doi.org/10.1006/hbeh.1999.1535. PMid:10506541.

Mayeaux DJ, Wallace MB, Young AM. Effect of nutrient restriction on social transmission of food preferences depends on nutrient and species. J Behav Brain Sci. 2014;04(12):590-601. http://doi.org/10.4236/jbbs.2014.412056.

McIntosh TK, Barfield RJ. The temporal patterning of 40–60 kHz ultrasonic vocalizations and copulation in the rat (Rattus norvegicus). Behav Neural Biol. 1980;29(3):349-58. http://doi.org/10.1016/S0163-1047(80)90259-9.

Moreira N, Bernardi MM, Spinosa HS. Ivermectin reduces sexual behavior in female rats. Neurotoxicol Teratol. 2014;43:33-8. http://doi.org/10.1016/j.ntt.2014.03.003. PMid:24681284.

Moreira N, Sandini TM, Reis-Silva TM, Navas-Suáresz P, Auada AVV, Lebrun I, Flório JC, Bernardi MM, Spinosa HS. Ivermectin reduces motor coordination, serum testosterone, and central neurotransmitter levels but does not affect sexual motivation in male rats. Reprod Toxicol. 2017;74:195-203. http://doi.org/10.1016/j.reprotox.2017.10.002. PMid:29055807.

Peters SM, Tuffnell JA, Pinter IJ, van der Harst JE, Spruijt BM. Short- and long-term behavioral analysis of social interaction, ultrasonic vocalizations and social motivation in a chronic phencyclidine model. Behav Brain Res. 2017;325(Pt A):34-43. http://doi.org/10.1016/j.bbr.2017.02.027. PMid:28235589.

Reynolds DS, Wayman CP. Animal models of sexual function. In: Koob GF, Moal M, Thompson RF, editors. Encyclopedia of behavioral neuroscience. London: Elsevier; 2010. p. 83-9. http://doi.org/10.1016/B978-0-08-045396-5.00020-8.

Riaz MS, Bohlen MO, Gunter BW, Quentin Q, Stockmeier CA, Paul IA. Attenuation of social interaction-associated ultrasonic vocalizations and spatial working memory performance in rats exposed to chronic unpredictable stress. Physiol Behav. 2015;152(Pt A):128-34. http://doi.org/10.1016/j.physbeh.2015.09.005. PMid:26367455.

Rodrigues-Alves PSB, Lebrun I, Flório JC, Bernardi MM, Spinosa HDS. Moxidectin interference on sexual behavior, penile erection and hypothalamic GABA levels of male rats. Res Vet Sci. 2008;84(1):100-6. http://doi.org/10.1016/j.rvsc.2007.04.003. PMid:17559896.

Scattoni ML, Crawley J, Ricceri L. Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders. Neurosci Biobehav Rev. 2009;33(4):508-15. http://doi.org/10.1016/j.neubiorev.2008.08.003. PMid:18771687.

Shoop WL, Mrozik H, Fisher MH. Structure and activity of avermectins and milbemycins in animal health. Vet Parasitol. 1995;59(2):139-56. http://doi.org/10.1016/0304-4017(94)00743-V. PMid:7483237.

Snoeren EMS, Agmo A. The incentive value of males’ 50-kHz ultrasonic vocalizations for female rats (Rattus norvegicus). J Comp Psychol. 2014;128(1):40-55. http://doi.org/10.1037/a0033204. PMid:24040761.

Soll MD. Use of ivermectin in laboratory and exotic mammals and in birds, fish, and reptiles. In: Campbell WC, editor. Ivermectin and abamectin. New York: Springer; 1989. p. 260-86. http://doi.org/10.1007/978-1-4612-3626-9_19.

Spinosa HS, Gerenutti M, Bernardi MM. Anxiolytic and anticonvulsant properties of doramectin in rats: behavioral and neurochemistric evaluations. Comp Biochem Physiol C Toxicol Pharmacol. 2000;127(3):359-66. http://doi.org/10.1016/S0742-8413(00)00165-1. PMid:11246508.

Willadsen M, Seffer D, Schwarting RKW, Wöhr M. Rodent ultrasonic communication: male pro-social 50-kHz ultrasonic vocalizations elicit social approach behavior in female rats (Rattus norvegicus). J Comp Psychol. 2014;128(1):56-64. http://doi.org/10.1037/a0034778. PMid:24188619.

Wolstenholme AJ, Rogers AT. Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology. 2005;131(Suppl 1):S85-95. http://doi.org/10.1017/S0031182005008218. PMid:16569295.

Yang C-C. Acute human toxicity of macrocyclic lactones. Curr Pharm Biotechnol. 2012;13(6):999-1003. http://doi.org/10.2174/138920112800399059. PMid:22039794.

Zarrindast M-R, Farahvash H. Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats. Psychopharmacology. 1994;115(1-2):249-53. http://doi.org/10.1007/BF02244779. PMid:7862903.

Downloads

Published

2023-03-20

Issue

Section

FULL ARTICLE

Funding data

How to Cite

1.
Rodrigues P da S, Sampaio ACS, Silva Éricka P da, Suffredini IB, Bondan EF, Bernardi MM, et al. Sexual motivation and performance in sexual naïve and experienced rats treated with ivermectin: an ultrasonic vocalization study. Braz. J. Vet. Res. Anim. Sci. [Internet]. 2023 Mar. 20 [cited 2024 May 26];60:e198441. Available from: https://www.revistas.usp.br/bjvras/article/view/198441