Modelling sexual violence in male rats: the sexual aggression test (SxAT)

Biological Psychiatry; Cellular and Molecular Neuroscience; Psychiatry and Mental health; Sexual Violence; Aggresssion; Psychopathology; Oxytocin; Decision-making

Abstract :

[en] Sexual assault and rape are crimes that impact victims worldwide. Although the psychosocial and eco-evolutionary factors associated with this antisocial behavior have repeatedly been studied, the underlying neurobiological mechanisms are still largely unknown. Here, we established a novel paradigm to provoke and subsequently assess sexual aggression (SxA) in adult male Wistar rats: the sexual aggression test (SxAT). Briefly, male Wistar rats are sexually aroused by a receptive female, which is exchanged by a non-receptive female immediately after the first intromission. This protocol elicits forced mounting and aggressive behavior toward the non-receptive female to different degrees, which can be scored. In a series of experiments we have shown that SxA behavior is a relatively stable trait in rats and correlates positively with sexual motivation. Rats with innate abnormal anxiety and aggressive behavior also show abnormal SxA behavior. In addition, central infusion of oxytocin moderately inhibits aggressive behavior, but increases forced mounting. Finally, we identified the agranular insular cortex to be specifically activated by SxA, however, inhibition of this region did not significantly alter behavior in the SxAT. Altogether, the SxAT is a paradigm that can be readily implemented in behavioral laboratories as a valuable tool to find answers regarding the biological mechanisms underlying SxA in humans, as well as social decision-making in general.

Disciplines :

Life sciences: Multidisciplinary, general & others

Author, co-author :

De Moura Oliveira, Vinicius Elias ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau

de Jong, Trynke R.

Neumann, Inga D.

Language :

English

Title :

Modelling sexual violence in male rats: the sexual aggression test (SxAT)

Publication date :

18 May 2022

Journal title :

Translational Psychiatry

eISSN :

2158-3188

Publisher :

Springer Science and Business Media LLC

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.nature.com/articles/s41398-022-01973-3.pdf

Name of the research project :

EC | Horizon 2020 Framework Programme

Funders :

DFG - Deutsche Forschungsgemeinschaft

Available on ORBi :

since 18 May 2022

Statistics

Number of views

44 (2 by ULiège)

Number of downloads

21 (1 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

WHO. Violence against Women: Prevalence estimates, 2018: Global, regional and national prevalence estimates for intimate partner violence against women and global and regional prevalence estimates for non-partner sexual violence against women. World Health Organization (WHO). https://www.who.int/health-topics/violence-against-women. 2021.
EIGE. Gender-based violence. 2021. https://eige.europa.eu/gender-based-violence/what-is-gender-based-violence.
Campbell JC. Health consequences of intimate partner violence. Lancet. 2002;359:1331–6.
Campbell R, Dworkin E, Cabral G. An ecological model of the impact of sexual assault on women’s mental health. Trauma Violence Abus. 2009;10:225–46.
Lösel F, Schmucker M. The effectiveness of treatment for sexual offenders: a comprehensive meta-analysis. J Exp Criminol. 2005;1:117–46.
Hanson RK, Morton-Bourgon KE. The Accuracy of Recidivism Risk Assessments for Sexual Offenders: a Meta-Analysis of 118 Prediction Studies. Psychol Assess. 2009;21:1–21.
Smid WJ, Kamphuis JH, Wever EC, Van, Beek DJ. A comparison of the predictive properties of nine sex offender risk assessment instruments. Psychol Assess. 2014;26:691–703.
Smuts BB, Smuts RW. Male Aggression and Sexual Coercion of Females in Nonhuman Primates and Other Mammals: Evidence and Theoretical Implications. Adv Study Behav. 1993;22:1–63.
Baxter CM, Yan JL, Dukas R. Genetic variation in sexual aggression and the factors that determine forced copulation success. Anim Behav. 2019;158:261–7.
Cassini MH. Sexual aggression in mammals. Mamm Rev. 2021;51:247–55.
Shors TJ, Tobon K, Difeo G, Durham DM, Chang HYM. Sexual Conspecific Aggressive Response (SCAR): A Model of Sexual Trauma that Disrupts Maternal Learning and Plasticity in the Female Brain. Sci Rep. 2016;6:1–11.
Lussier P, Cale J. Understanding the origins and the development of rape and sexual aggression against women: Four generations of research and theorizing. Aggress Violent Behav. 2016;31:66–81.
Thornhill R and Palmer C. A Natural History of Rape: Biological Bases of Sexual Coercion. Cambridge:MIT Press;2000.
Chen CY, Raine A, Chou KH, Chen IY, Hung D, Lin CP. Abnormal white matter integrity in rapists as indicated by diffusion tensor imaging. BMC Neurosci. 2016;17:1–8.
Raine A. The neuromoral theory of antisocial, violent, and psychopathic behavior. Psychiatry Res. 2019;277:64–9.
Turner D, Briken P. Treatment of Paraphilic Disorders in Sexual Offenders or Men With a Risk of Sexual Offending With Luteinizing Hormone-Releasing Hormone Agonists: An Updated Systematic Review. J Sex Med. 2018;15:77–93.
Kingston DA, Seto MC, Ahmed AG, Fedoroff P, Firestone P, Bradford JM. The role of central and peripheral hormones in sexual and violent recidivism in sex offenders. J Am Acad Psychiatry Law. 2012;40:476–85.
Masis-Calvo M, Schmidtner AK, Oliveira VEM, Grossmann CP, de Jong TR, Neumann ID. Animal models of social stress: the dark side of social interactions. Stress. 2018;5:41–432.
Lukas M, de Jong TR. Conspecific Interactions in Adult Laboratory Rodents: Friends or Foes? In: Wöhr M, Krach S, editors. Social Behavior from Rodents to Humans: Neural Foundations and Clinical Implications. Cham:Springer International Publishing;2017. 3–24.
Henniger MSH, Ohl F, Hölter SM, Weißenbacher P, Toschi N, Lörscher P, et al. Unconditioned anxiety and social behaviour in two rat lines selectively bred for high and low anxiety-related behaviour. Behav Brain Res. 2000;111:153–63.
Neumann ID, Veenema AH, Beiderbeck DI. Aggression and anxiety: social context and neurobiological links. Front Behav Neurosci. 2010;4:1–12.
de Jong TR, Neumann ID. Oxytocin and Aggression. Curr Top Behav Neurosci. 2017;35:1–18.
Lukas M, Toth I, Reber SO, Slattery DA, Veenema AH, Neumann ID. The neuropeptide oxytocin facilitates pro-social behavior and prevents social avoidance in rats and mice. Neuropsychopharmacology. 2011;36:2159–68.
Argiolas A, Melis MR. Neuropeptides and central control of sexual behaviour from the past to the present: a review. Prog Neurobiol. 2013;108:80–107.
Calcagnoli F, De Boer SF, Althaus M, Den Boer JA, Koolhaas JM. Antiaggressive activity of central oxytocin in male rats. Psychopharmacol (Berl). 2013;229:639–51.
Oliveira VEM, Lukas M, Wolf HN, Durante E, Lorenz A, Mayer A-L, et al. Oxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats. Nat Commun. 2021;12:1–15.
De Jong TR, Beiderbeck DI, Neumann ID. Measuring virgin female aggression in the Female Intruder Test (FIT): Effects of oxytocin, estrous cycle, and anxiety. PLoS ONE. 2014;9:e91701.
Beiderbeck DI, Neumann ID, Veenema AH. Differences in intermale aggression are accompanied by opposite vasopressin release patterns within the septum in rats bred for low and high anxiety. Eur J Neurosci. 2007;26:3597–605.
Abbey A, Zawacki T, Buck PO, Monique Clinton A, McAuslan P. Alcohol and sexual assault. Alcohol Res Heal. 2001;25:43–51.
Terranova JI, Song Z, Larkin TE, Hardcastle N, Norvelle A, Riaz A, et al. Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain. Proc Natl Acad Sci USA. 2016;113:13233–8.
Oliveira VEM, Neumann ID, de Jong TR. Post-weaning social isolation exacerbates aggression in both sexes and affects the vasopressin and oxytocin system in a sex-specific manner. Neuropharmacology. 2019;156:107504.
Veenema AH, Beiderbeck DI, Lukas M, Neumann ID. Distinct correlations of vasopressin release within the lateral septum and the bed nucleus of the stria terminalis with the display of intermale aggression. Horm Behav. 2010;58:273–81.
Tan O, Musullulu H, Raymond JS, Wilson B, Langguth M, Bowen MT. Oxytocin and vasopressin inhibit hyper-aggressive behaviour in socially isolated mice. Neuropharmacology. 2019;156:107573.
De Almeida RMM, Miczek KA. Aggression escalated by social instigation or by discontinuation of reinforcement (‘Frustration’) in mice: Inhibition by anpirtoline: A 5-HT1B receptor agonist. Neuropsychopharmacology. 2002;27:171–81.
Miczek KA, De Boer SF, Haller J. Excessive aggression as model of violence: a critical evaluation of current preclinical methods. Psychopharmacol (Berl). 2013;226:445–58.
Pfaus JG, Pinel JPJ. Alcohol inhibits and disinhibits sexual behavior in the male rat. Psychobiology. 1989;17:195–201.
Karigo T, Kennedy A, Yang B, Liu M, Tai D, Wahle IA, et al. Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice. Nature 2020;589. https://doi.org/10.1038/s41586-020-2995-0.
Laman-Maharg A, Trainor BC. Stress, sex, and motivated behaviors. J Neurosci Res. 2017;95:83–92.
Wei D, Talwar V, Lin D. Neural circuits of social behaviors: Innate yet flexible. Neuron. 2021;109:1600–20.
Lenschow C, Lima SQ. In the mood for sex: neural circuits for reproduction. Curr Opin Neurobiol. 2020;60:155–68.
Nelson RJ, Trainor BC. Neural Mechanisms of Aggression. Nat Rev Neurosci. 2007;8:536–46.
Nieuwenhuys R. The insular cortex. A review. 1st ed. Elsevier B.V.; 2012. https://doi.org/10.1016/B978-0-444-53860-4.00007-6.
Rogers-Carter MM, Christianson JP. An insular view of the social decision-making network. Neurosci Biobehav Rev. 2019;103:119–32.
Koolhaas JM, Coppens CM, de Boer SF, Buwalda B, Meerlo P, Timmermans PJ. The resident-intruder paradigm: a standardized test for aggression, violence and social stress. J Vis Exp. 2013;77:4367.
Koolhaas JM, Schuurman T, Wiepkema PR. The organization of intraspecific agonistic behaviour in the rat. Prog Neurobiol. 1980;15:247–68.
Blumstein DT, Evans CS, Daniel JC JWatcher 0.9: An Introductory User’s Guide. Anim. Behav. Lab. Macquarie Univ.; 2000.
de Jong TR, Neumann ID. Moderate Role of Oxytocin in the Pro-Ejaculatory Effect of the 5-HT1AReceptor Agonist 8-OH-DPAT. J Sex Med. 2015;12:17–28.
Nyuyki KD, Waldherr M, Baeuml S, Neumann ID. Yes, I am ready now: differential effects of paced versus unpaced mating on anxiety and central oxytocin release in female rats. PLoS ONE. 2011;6:e23599.
Beiderbeck DI, Reber SO, Havasi A, Bredewold R, Veenema AH, Neumann ID. High and abnormal forms of aggression in rats with extremes in trait anxiety — Involvement of the dopamine system in the nucleus accumbens. Psychoneuroendocrinology. 2012;37:1969–80.
Veenema AH, Bredewold R, Neumann ID. Opposite effects of maternal separation on intermale and maternal aggression in C57BL/6 mice: Link to hypothalamic vasopressin and oxytocin immunoreactivity. Psychoneuroendocrinology. 2007;32:437–50.
Barbaro N, Parkhill MR, Nguyen D. Anxious and Hostile: Consequences of Anxious Adult Attachment in Predicting Male-Perpetrated Sexual Assault. J Interpers Violence. 2018;33:2098–117.
Ferris CF, Melloni RH Jr, Koppel G, Perry KW, Fuller RW, Delville Y. Vasopressin/Serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. J Neurosci. 1997;17:4331–40.
Dumais KM, Veenema AH. Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior. Front Neuroendocrinol. 2016;40:1–23.
Insel TR. The Challenge of Translation in Social Neuroscience: a Review of Oxytocin, Vasopressin, and Affiliative Behavior. Neuron. 2010;65:768–79.
Winter J, Meyer M, Berger I, Royer M, Bianchi M, Kuffner K, et al. Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety. Mol Psychiatry 2021. 10.1038/s41380-021-01141-x.
Neumann ID, Slattery DA. Oxytocin in General Anxiety and Social Fear: a translational approach. Biol Psychiatry. 2016;79:213–21.
Blume A, Bosch OJ, Miklos S, Torner L, Wales L, Waldherr M, et al. Oxytocin reduces anxiety via ERK1/2 activation: local effect within the rat hypothalamic paraventricular nucleus. Eur J Neurosci. 2008;27:1947–56.
Jurek B, Neumann ID. The oxytocin receptor: from intracellular signaling to behavior. Physiol Rev. 2018;98:1805–908.
Yamagishi A, Lee J, Sato N. Oxytocin in the anterior cingulate cortex is involved in helping behaviour. Behav Brain Res. 2020;393:112790.
Paulussen M, Jacobs S, Van Der Gucht E, Hof PR, Arckens L. Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit. Brain Struct Funct. 2011;216:183–99.
Cordero MI, Moser DA, Manini A, Suardi F, Sancho-Rossignol A, Torrisi R, et al. Effects of interpersonal violence-related post-traumatic stress disorder (PTSD) on mother and child diurnal cortisol rhythm and cortisol reactivity to a laboratory stressor involving separation. Horm Behav. 2017;90:15–24.
Harris AZ, Atsak P, Bretton ZH, Holt ES, Alam R, Morton MP, et al. A Novel Method for Chronic Social Defeat Stress in Female Mice. Neuropsychopharmacology. 2018;43:1276–83.
Lopez J, Bagot RC. Defining Valid Chronic Stress Models for Depression With Female Rodents. Biol Psychiatry. 2021;90:226–35.
Newman EL, Covington HE III, Suh J, Bicakci MB, Ressler KJ, Debold JF, et al. Fighting females: Neural and behavioral consequences of social defeat stress in female mice. Biol Psychiatry. 2019;86:657–68.