Knockdown of sexually differentiated vasopressin expression in the bed nucleus of the stria terminalis reduces social and sexual behaviour in male, but not female, mice
Open accessAbstract
The neuropeptide arginine-vasopressin (AVP) has long been implicated in the regulation of social behaviour and communication, but the sources of AVP release relevant for behaviour have not been precisely determined. Ablations of the sexually dimorphic AVP cells within the bed nucleus of the stria terminalis (BNST), which are more numerous in males, affect social behaviour differently in males and females. However, it is unknown whether these behavioural effects are caused by a reduction of AVP or of other factors associated with these cells. To test the role of AVP specifically, we used an shRNA viral construct to knock down AVP gene expression within the BNST of wild-type male and female mice, using scrambled sequence virus as a control, and evaluated subsequent changes in social behaviours (social investigation, ultrasonic vocalization (USV), scent marking, copulation, and aggression), or anxiety-like behaviours (elevated plus maze). We observed that, in males, knockdown of AVP expression in the BNST strongly reduced investigation of novel males, aggressive signalling towards other males (tail rattling, USV), and copulatory behaviour, but did not alter attack initiation, other measures of social communication, or anxiety-like behaviours. In females, however, BNST AVP knockdown did not alter any of these behaviours. These results point to differential involvement of AVP derived from the BNST in social behaviour.
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The appetitive and consummatory aspects of sex are regulated by gonadal steroids (estrogen, progesterone, testosterone) as well as by OT, DA, and AVP.
“The appetitive and consummatory aspects of sex are regulated by gonadal steroids (estrogen, progesterone, testosterone) as well as by OT, DA, and AVP [51,119,120,121,122].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [51]
The Discussion reports that BNST AVP knockdown reduced intromissions and ejaculations in male mice and may impair the transition between appetitive and consummatory phases. The Methods describe estradiol and progesterone treatment to induce sexual receptivity in stimulus females. Our copy does not establish the sentence’s broader claim that both phases are regulated by all the listed hormones and by OT and DA. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn male but not female mice, AVP cells in the BNST and MeA are active during mating, and knockdown of BNST AVP cells inhibits male sexual behaviors.
“In male but not female mice, AVP cells in the BNST and MeA are active during mating, and the knockdown of BNST AVP cells inhibits male sexual behaviors [48,51].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [51]
The Discussion reports that BNST and MeA AVP cells are active during male copulatory behaviour, and that BNST AVP knockdown reduced intromissions and ejaculations in males but not females. It does not say those cells are inactive during female mating. The intervention knocked down AVP expression in BNST cells, rather than knocking down the cells themselves; page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredRodent studies of mating suggest a sexually dimorphic role of AVP in sexual behavior.
“Rodent studies of mating suggest a sexually dimorphic role of AVP in sexual behavior.”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [51]
Arginine vasopressin has been linked to parental nurturing.
“In addition to the effects of OT and DA in promoting parental care of both sexes, AVP, known to promote territoriality, aggression, and mating, has been linked to parental nurturing [48,49,50,51].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [51]
The Introduction links AVP to social behaviour and communication, and the Methods > Social behaviour section describes tests of social investigation, mating, and aggression (page numbers unavailable). Searches for parental care, nurturing, and care of offspring found no passage linking AVP to parental nurturing. (LLM, conf=0.76)
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“Previously, however, we have shown that blocking AVP synthesis in BNST cells reduces the same behaviors that are blocked by optogenetic inhibition in this study (26), supporting the idea that changes in AVP release play an important role in the changes observed in this study.”
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Cooper, M., Hooker, M. K., Whitten, C. J., Kelly, J. R., Jenkins, M. S., Mahometano, S. C., & Scarbrough, M. C. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114628 · Cited by 9 · see citing works
Breach, M. R., Akouri, H. E., Costantine, S., Dodson, C. M., McGovern, N., & Lenz, K. M. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2023.105427 · Cited by 10 · see citing works
Arakawa, H., & Higuchi, Y. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104597 · Cited by 8 · see citing works
Bortolozzo-Gleich, M. H., Bouisset, G., Geng, L., Pino, A. R., Nomura, Y., Han, S., Li, Y., & Leroy, F. (2025) · Nature Communications · doi:10.1038/s41467-025-61994-6 · Cited by 9 · see citing works
Lakhssassi, K., Sarto, P., Marín, B., Crespo, B. L., Folch, J., Alabart, J. L., Serrano, M., & Calvo, J. H. (2022) · Journal of Animal Science · doi:10.1093/jas/skac365 · Cited by 8 · see citing works
Naloxone increases conditioned fear responses during social buffering in male rats
Yamasaki, T., Kiyokawa, Y., Munetomo, A., & Takeuchi, Y. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16343 · Cited by 7 · see citing works
“A similar effect was observed in vasopressin gene – knock-down male mice (Rigney et al., 2022).”
ResultThe regulative role and mechanism of BNST in anxiety disorder
Xie, M., Xiong, Y., & Wang, H. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1437476 · Cited by 7 · see citing works
Fu, P., Liu, C.-P., Liu, C.-Y., Zhang, Y.-C.-F., Xu, J.-P., Mao, R.-T., Ding, X., Li, F., Zhang, Y.-L., Yang, H., et al. (2025) · Research · doi:10.34133/research.0701 · Cited by 7 · see citing works
“The shRNA(AVP) target sequence was from a previous study and demonstrated 91% knockdown in vitro [ 86 ].”
Court, L., Talbottier, L., Lemarchand, J., Cornilleau, F., Pecnard, E., Blache, M., Balthazart, J., Cornil, C. A., Keller, M., Calandreau, L., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-74906-3 · Cited by 5 · see citing works
Friesen, C. N., Hartswick, D., Selke, A., Vries, G. J. D., & Petrulis, A. (2025) · Hormones and Behavior · doi:10.1016/j.yhbeh.2025.105792 · Cited by 2 · see citing works
Aspesi, D., Varatharajah, A., Cioffi, L., Diviccaro, S., Caruso, D., Becke, N., Lalonde, J., Perreault, M. L., Melcangi, R. C., MacLusky, N. J., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2600302123 · Cited by 2 · see citing works
Sexual behavior and drive: Is it all in your brain?
Zilkha, N., & Kimchi, T. (2023) · Current Biology · doi:10.1016/j.cub.2023.09.029 · Cited by 2 · see citing works
Cui, Y. X., Guo, M. L., Ren, J. Q., Yang, J., Miao, Y. X., Wei, J., Zhang, Z. Y., He, F., Wang, B., & Wang, Z. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114997 · Cited by 1 · see citing works
Yuan, H., Zhong, Y., & Zhang, X. (2026) · Cells · doi:10.3390/cells15020116 · Cited by 1 · see citing works
“Vasopressin (AVP)-expressing neurons in the BNST are crucial for social investigation and recognition [44,65], while the oxytocin (OT) system in the anteromedial BNST plays a key role in stress-induced social avoidance [66,67].”
Tail-rattling in rodents: more than a threat display
d’Isa, R., Bębas, P., Parsons, M. H., Kurek, K., & Stryjek, R. (2026) · Journal of Comparative Physiology A · doi:10.1007/s00359-026-01808-2 · Cited by 1 · see citing works
Altered vocal communication in adult vasopressin-deficient Brattleboro rats
Cordes, C. N., Fredricks, C. P., Liu, L., Brakey, D. J., Daniels, D., & Paul, M. J. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114699 · Cited by 1 · see citing works
A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in micePreprint
Rigney, N., Campos‐Lira, E., Kirchner, M. K., Wei, W., Belkasim, S., Beaumont, R., Singh, S. P., Vries, G. J. D., & Petrulis, A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.06.564847 · Cited by 1 · see citing works
Eiden, L. E., & Zhang, L. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13183
Naloxone blocks social buffering of conditioned fear responses in ratsPreprint
Yamasaki, T., Kiyokawa, Y., Munetomo, A., & Takeuchi, Y. (2023) · doi:10.22541/au.168434829.95000136/v1
Kelly, A. M. (2025) · Hormones and Behavior · doi:10.1016/j.yhbeh.2025.105763
Advancing insights into the neuroendocrine basis of socio-sexual interactions in mammals
Masoumparast, M., Fiset, J.-P., Nasri, N., & Silva, M. S. B. (2026) · Endocrinology · doi:10.1210/endocr/bqag036
Nonlinear and sex-specific effects of V1aR deletion on juvenile social behavior
Aspesi, D., Vu, H., Rivers, I., Stoehr, M., Huhman, K. L., & Albers, H. E. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1901426
- Authors
- Rigney, N., Zbib, A., de Vries, G. J., & Petrulis, A.
- Affiliations
- Georgia State University (US)
- Center for Behavioral Neuroscience Neuroscience Institute Georgia State University Atlanta Georgia USA
- Corresponding author
- Rigney, Nicole
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2022-01-02
- Volume
- 34
- Issue
- 9
- Pages
- e13083-e13083
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- PMC
- PMC9213575
- OpenAlex
- W4200399209
- Cited by
- 29
- References
- 83
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 1
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroendocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (F31 MH125659, R01 MH121603)
- Georgia State University
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- vasopressin, bed nucleus of the stria terminalis, sexually dimorphic neurons, social behavior, sexual behavior, social investigation, ultrasonic vocalizations, aggression, copulation, scent marking, anxiety-like behavior, shRNA knockdown, sex differences
- MeSH terms
- Animals, Arginine, Arginine Vasopressin, Female, Male, Septal Nuclei, Vasopressins, RNA, Small Interfering, Mice
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