Pantouli, F;
Pujol, CN;
Derieux, C;
Fonteneau, M;
Pellissier, LP;
Marsol, C;
Karpenko, J;
Bonnet, D;
Hibert, M;
Bailey, A;
et al.
Pantouli, F; Pujol, CN; Derieux, C; Fonteneau, M; Pellissier, LP; Marsol, C; Karpenko, J; Bonnet, D; Hibert, M; Bailey, A; Le Merrer, J; Becker, JAJ
(2024)
Acute, chronic and conditioned effects of intranasal oxytocin in the mu-opioid receptor knockout mouse model of autism: Social context matters.
Neuropsychopharmacology.
ISSN 0893-133X
https://doi.org/10.1038/s41386-024-01915-1
SGUL Authors: Bailey, Alexis
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Abstract
Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behaviours. Multiple studies have highlighted the potential of oxytocin (OT) to ameliorate behavioural abnormalities in animal models and subjects with ASD. Clinical trials, however, yielded disappointing results. Our study aimed at assessing the behavioural effects of different regimens of OT administration in the Oprm1 null mouse model of ASD. We assessed the effects of intranasal OT injected once at different doses (0.15, 0.3, and 0.6 IU) and time points (5, 15, and 30 min) following administration, or chronically, on ASD-related behaviours (social interaction and preference, stereotypies, anxiety, nociception) in Oprm1+/+ and Oprm1-/- mice. We then tested whether pairing intranasal OT injection with social experience would influence its outcome on ASD-like symptoms, and measured gene expression in the reward/social circuit. Acute intranasal OT at 0.3 IU improved social behaviour in Oprm1-/- mice 5 min after administration, with limited effects on non-social behaviours. Chronic (8–17 days) OT maintained rescuing effects in Oprm1 null mice but was deleterious in wild-type mice. Finally, improvements in the social behaviour of Oprm1-/- mice were greater and longer lasting when OT was administered in a social context. Under these conditions, the expression of OT and vasopressin receptor genes, as well as marker genes of striatal projection neurons, was suppressed. We detected no sex difference in OT effects. Our results highlight the importance of considering dosage and social context when evaluating the effects of OT treatment in ASD.
Item Type: | Article | ||||||
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Additional Information: | © The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | ||||||
Keywords: | 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Psychiatry | ||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical & Biomedical Education (IMBE) Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE) Academic Structure > REF 2021 user group |
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Journal or Publication Title: | Neuropsychopharmacology | ||||||
ISSN: | 0893-133X | ||||||
Language: | en | ||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/116688 | ||||||
Publisher's version: | https://doi.org/10.1038/s41386-024-01915-1 |
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