{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:00:56Z","timestamp":1786122056582,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1231556"],"award-info":[{"award-number":["1231556"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1231556"],"award-info":[{"award-number":["1231556"]}],"id":[{"id":"https:\/\/ror.org\/016nafs32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mating influences the physiology of female animals and induces changes in behaviors associated with securing resources for their offspring. Modulatory neurotransmitters are known to adjust behavioral responses of animals according to environmental cues and internal physiological states. In that regard, it has been shown that serotonin (5-HT) modulates some post-mating behavioral features in Drosophila. However, it remains unknown whether serotonin regulates post-mating social behavior or responses to food cues in flies, which are among several behaviors that serve to secure their survival and reproduction. Here, we report a behavioral paradigm, the yeast-response test (YRT), for exploring locomotor and social behavioral changes in groups of virgin and mated females using yeast odor as a naturalistic food signal. Using this setup, we found that exposure to yeast odor increases social interactions in mated but not virgin females under non-aversive conditions and that these responses are suppressed at aversive temperatures. Furthermore, chronic impairment of serotonin transporter function reverses the social behavioral response to food odor in mated females, without affecting their olfactory capacity. Whole-brain 5-HT content, as well as histone serotonylation, were unchanged between virgin and mated females, suggesting that 5-HT contribution to these changes is mediated at a circuit level rather than by global neuromodulatory mechanisms. Consistent with this idea, silencing serotonin projection neurons (SPNs) selectively abolished mating-induced changes in social behavior without affecting the locomotor effects. These results provide further support for data in the literature showing that SPNs belong to a discrete circuit underlying social behaviors in female flies. Together, these results support a model in which serotonergic signaling shapes post-mating behavior in Drosophila through functionally segregated neural circuits.<\/jats:p>","DOI":"10.3390\/ijms27167070","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:01:36Z","timestamp":1786089696000},"page":"7070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mating-Induced Behavioral Changes in Female Drosophila Are Modulated by Serotonin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-7299","authenticated-orcid":false,"given":"Sim\u00f3n","family":"Guerra-Ayala","sequence":"first","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2788-5183","authenticated-orcid":false,"given":"Antonella","family":"Cort\u00e9s-Henott","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9009-153X","authenticated-orcid":false,"given":"Paula","family":"Amado-Hinojosa","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-9333","authenticated-orcid":false,"given":"Marcia","family":"Gonz\u00e1lez-Teuber","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-193X","authenticated-orcid":false,"given":"Ivana","family":"Gajardo","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-8340","authenticated-orcid":false,"given":"Jorge M.","family":"Campusano","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1016\/j.neuron.2021.09.055","article-title":"Olfactory landmarks and path integration converge to form a cognitive spatial map","volume":"109","author":"Clark","year":"2021","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s41745-017-0053-1","article-title":"Navigational Strategies and Their Neural Correlates","volume":"97","author":"Jain","year":"2017","journal-title":"J. Indian Inst. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Burnett, J.W., Ohnstad, H., Jones, A.M., Hardege, J.D., and Bartels-Hardege, H.D. (2026). Olfactory Cues in the Odour Plume of Predatory Fish Reduce Foraging and Elicit Anti-Predator Behaviour in the European Green Crab Carcinus maenas. Animals, 16.","DOI":"10.3390\/ani16050828"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00441-020-03395-3","article-title":"Spatial information from the odour environment in mammalian olfaction","volume":"383","author":"Marin","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gajardo, I., Guerra, S., and Campusano, J.M. (2023). Navigating Like a Fly: Drosophila melanogaster as a Model to Explore the Contribution of Serotonergic Neurotransmission to Spatial Navigation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054407"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e08688","DOI":"10.7554\/eLife.08688","article-title":"Food odors trigger Drosophila males to deposit a pheromone that guides aggregation and female oviposition decisions","volume":"4","author":"Lin","year":"2015","journal-title":"eLife"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00359-022-01611-9","article-title":"Olfactory navigation in arthropods","volume":"209","author":"Steele","year":"2023","journal-title":"J. Comp. Physiol. A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1126\/science.1253291","article-title":"Neural control of maternal and paternal behaviors","volume":"345","author":"Dulac","year":"2014","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1210\/en.2009-1385","article-title":"Prolactin-Induced Mitogenesis in the Subventricular Zone of the Maternal Brain during Early Pregnancy Is Essential for Normal Postpartum Behavioral Responses in the Mother","volume":"151","author":"Larsen","year":"2010","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.cub.2012.04.062","article-title":"Neural Circuitry Underlying Drosophila Female Postmating Behavioral Responses","volume":"22","author":"Pavlou","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1007\/s11064-019-02722-7","article-title":"The Effect of Mating and the Male Sex Peptide on Group Behaviour of Post-mated Female Drosophila melanogaster","volume":"44","author":"Isaac","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaax3432","DOI":"10.1126\/sciadv.aax3432","article-title":"A sperm peptide enhances long-term memory in female Drosophila","volume":"5","author":"Scheunemann","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3109\/01677063.2012.666298","article-title":"Serotonin is Critical for Rewarded Olfactory Short-Term Memory in Drosophila","volume":"26","author":"Sitaraman","year":"2012","journal-title":"J. Neurogenet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Xu, L., He, J., Kaiser, A., Gr\u00e4ber, N., Schl\u00e4ger, L., Ritze, Y., and Scholz, H. (2016). A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila. PLoS ONE, 11, Erratum in PLoS ONE\u00a02017, 12, e0174010.","DOI":"10.1371\/journal.pone.0174010"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s12264-022-00908-8","article-title":"Serotonin Signaling Modulates Sexual Receptivity of Virgin Female Drosophila","volume":"38","author":"Ma","year":"2022","journal-title":"Neurosci. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106123","DOI":"10.1016\/j.isci.2023.106123","article-title":"Sex peptide regulates female receptivity through serotoninergic neurons in Drosophila","volume":"26","author":"Yang","year":"2023","journal-title":"iScience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41586-019-1024-7","article-title":"Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3","volume":"567","author":"Farrelly","year":"2019","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ostrowski, D., Salari, A., Zars, M., and Zars, T. (2018). A biphasic locomotor response to acute unsignaled high temperature exposure in Drosophila. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198702"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1038\/s41467-021-22322-w","article-title":"Robustness and plasticity in Drosophila heat avoidance","volume":"12","author":"Levy","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1016\/j.cub.2019.10.042","article-title":"Serotonergic Modulation of Walking in Drosophila","volume":"29","author":"Howard","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1021\/acschemneuro.7b00089","article-title":"Characterization of a Novel Drosophila SERT Mutant: Insights on the Contribution of the Serotonin Neural System to Behaviors","volume":"8","author":"Hidalgo","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ng2029","article-title":"Serotonin and neuropeptide F have opposite modulatory effects on fly aggression","volume":"39","author":"Dierick","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Monier, M., N\u00f6bel, S., Danchin, E., and Isabel, G. (2019). Dopamine and Serotonin Are Both Required for Mate-Copying in Drosophila melanogaster. Front. Behav. Neurosci., 12.","DOI":"10.3389\/fnbeh.2018.00334"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13072-025-00653-y","article-title":"Interaction of serotonin transporter and TGFB1 facilitates histone serotonylation-mediated synaptic plasticity following environmental enrichment in stressed mouse Mus booduga","volume":"19","author":"Sowndharya","year":"2026","journal-title":"Epigenet. Chromatin"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41586-024-08371-3","article-title":"Bidirectional histone monoaminylation dynamics regulate neural rhythmicity","volume":"637","author":"Zheng","year":"2025","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ra61","DOI":"10.1126\/scisignal.2003970","article-title":"Transglutaminase-catalyzed protein-protein cross-linking suppresses the activity of the NF-kappaB-like transcription factor relish","volume":"6","author":"Shibata","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1111\/1365-2435.13214","article-title":"The developmental environment modulates mating-induced aggression and fighting success in adult female Drosophila","volume":"32","author":"Bath","year":"2018","journal-title":"Funct. Ecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e19920","DOI":"10.7554\/eLife.19920","article-title":"Internal states drive nutrient homeostasis by modulating exploration-exploitation trade-off","volume":"5","author":"Faisal","year":"2016","journal-title":"eLife"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cub.2010.03.061","article-title":"Sex Peptide Receptor and Neuronal TOR\/S6K Signaling Modulate Nutrient Balancing in Drosophila","volume":"20","author":"Ribeiro","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e58942","DOI":"10.7554\/eLife.58942","article-title":"Cell types and neuronal circuitry underlying female aggression in Drosophila","volume":"9","author":"Schretter","year":"2020","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12792","DOI":"10.1523\/JNEUROSCI.1638-15.2015","article-title":"Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila","volume":"35","author":"Pooryasin","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s40001-022-00838-1","article-title":"Autism-like behaviors regulated by the serotonin receptor 5-HT2B in the dorsal fan-shaped body neurons of Drosophila melanogaster","volume":"27","author":"Cao","year":"2022","journal-title":"Eur. J. Med. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuron.2012.09.010","article-title":"Neuromodulation of Neuronal Circuits: Back to the Future","volume":"76","author":"Marder","year":"2012","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.neuron.2018.03.032","article-title":"Dunce Phosphodiesterase Acts as a Checkpoint for Drosophila Long-Term Memory in a Pair of Serotonergic Neurons","volume":"98","author":"Scheunemann","year":"2018","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104753","DOI":"10.1016\/j.neuint.2020.104753","article-title":"The behavioral and neurochemical characterization of a Drosophila dysbindin mutant supports the contribution of serotonin to schizophrenia negative symptoms","volume":"138","author":"Hidalgo","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Z\u00e1rate, R.V., Hidalgo, S., Navarro, N., Molina-Mateo, D., Arancibia, D., Rojo-Cort\u00e9s, F., Oliva, C., Andr\u00e9s, M.E., Zamorano, P., and Campusano, J.M. (2022). An Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster. Cells, 11.","DOI":"10.3390\/cells11091544"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3109\/01677063.2012.729626","article-title":"Automated quantification of locomotion, social interaction, and mate preference in Drosophila mutants","volume":"26","author":"Iyengar","year":"2012","journal-title":"J. Neurogenet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Petrovi\u0107, M., Me\u0161trovi\u0107, A., Waldowski, R.A., and Vujnovi\u0107, A.F. (2023). A network-based analysis detects cocaine-induced changes in social interactions in Drosophila melanogaster. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0275795"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7070\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:04:26Z","timestamp":1786089866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":38,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167070"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167070","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}