Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice
Substance-induced social behavior deficits dramatically worsen the clinical outcome of substance use disorders; yet, the underlying mechanisms remain poorly understood. Herein, we investigated the role for the corticotropin-releasing factor receptor 1 (CRF1) in the acute sociability deficits induced...
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eLife Sciences Publications Ltd
2025-02-01
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| Online Access: | https://elifesciences.org/articles/100849 |
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| author | Alessandro Piccin Anne-Emilie Allain Jérôme M Baufreton Sandrine S Bertrand Angelo Contarino |
| author_facet | Alessandro Piccin Anne-Emilie Allain Jérôme M Baufreton Sandrine S Bertrand Angelo Contarino |
| author_sort | Alessandro Piccin |
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| description | Substance-induced social behavior deficits dramatically worsen the clinical outcome of substance use disorders; yet, the underlying mechanisms remain poorly understood. Herein, we investigated the role for the corticotropin-releasing factor receptor 1 (CRF1) in the acute sociability deficits induced by morphine and the related activity of oxytocin (OXY)- and arginine-vasopressin (AVP)-expressing neurons of the paraventricular nucleus of the hypothalamus (PVN). For this purpose, we used both the CRF1 receptor-preferring antagonist compound antalarmin and the genetic mouse model of CRF1 receptor-deficiency. Antalarmin completely abolished sociability deficits induced by morphine in male, but not in female, C57BL/6J mice. Accordingly, genetic CRF1 receptor-deficiency eliminated morphine-induced sociability deficits in male mice. Ex vivo electrophysiology studies showed that antalarmin also eliminated morphine-induced firing of PVN neurons in male, but not in female, C57BL/6J mice. Likewise, genetic CRF1 receptor-deficiency reduced morphine-induced firing of PVN neurons in a CRF1 gene expression-dependent manner. The electrophysiology results consistently mirrored the behavioral results, indicating a link between morphine-induced PVN activity and sociability deficits. Interestingly, in male mice antalarmin abolished morphine-induced firing in neurons co-expressing OXY and AVP, but not in neurons expressing only AVP. In contrast, in female mice antalarmin did not affect morphine-induced firing of neurons co-expressing OXY and AVP or only OXY, indicating a selective sex-specific role for the CRF1 receptor in opiate-induced PVN OXY activity. The present findings demonstrate a major, sex-linked, role for the CRF1 receptor in sociability deficits and related brain alterations induced by morphine, suggesting new therapeutic strategy for opiate use disorders. |
| format | Article |
| id | doaj-art-aed796591ca143ab871eb386e8ee0f3d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-aed796591ca143ab871eb386e8ee0f3d2025-02-05T13:34:14ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.100849Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male miceAlessandro Piccin0https://orcid.org/0000-0001-9566-3808Anne-Emilie Allain1Jérôme M Baufreton2https://orcid.org/0000-0002-2623-6375Sandrine S Bertrand3https://orcid.org/0000-0002-3020-7980Angelo Contarino4https://orcid.org/0000-0002-7286-6941Université de Bordeaux, INCIA, Bordeaux, France; CNRS, INCIA, Bordeaux, FranceUniversité de Bordeaux, INCIA, Bordeaux, France; CNRS, INCIA, Bordeaux, FranceUniversité de Bordeaux, IMN, Bordeaux, France; CNRS, IMN, Bordeaux, FranceUniversité de Bordeaux, INCIA, Bordeaux, France; CNRS, INCIA, Bordeaux, FranceUniversité de Bordeaux, INCIA, Bordeaux, France; CNRS, INCIA, Bordeaux, France; INSERM, T3S, UMR-S 1124, Université Paris Cité, Paris, FranceSubstance-induced social behavior deficits dramatically worsen the clinical outcome of substance use disorders; yet, the underlying mechanisms remain poorly understood. Herein, we investigated the role for the corticotropin-releasing factor receptor 1 (CRF1) in the acute sociability deficits induced by morphine and the related activity of oxytocin (OXY)- and arginine-vasopressin (AVP)-expressing neurons of the paraventricular nucleus of the hypothalamus (PVN). For this purpose, we used both the CRF1 receptor-preferring antagonist compound antalarmin and the genetic mouse model of CRF1 receptor-deficiency. Antalarmin completely abolished sociability deficits induced by morphine in male, but not in female, C57BL/6J mice. Accordingly, genetic CRF1 receptor-deficiency eliminated morphine-induced sociability deficits in male mice. Ex vivo electrophysiology studies showed that antalarmin also eliminated morphine-induced firing of PVN neurons in male, but not in female, C57BL/6J mice. Likewise, genetic CRF1 receptor-deficiency reduced morphine-induced firing of PVN neurons in a CRF1 gene expression-dependent manner. The electrophysiology results consistently mirrored the behavioral results, indicating a link between morphine-induced PVN activity and sociability deficits. Interestingly, in male mice antalarmin abolished morphine-induced firing in neurons co-expressing OXY and AVP, but not in neurons expressing only AVP. In contrast, in female mice antalarmin did not affect morphine-induced firing of neurons co-expressing OXY and AVP or only OXY, indicating a selective sex-specific role for the CRF1 receptor in opiate-induced PVN OXY activity. The present findings demonstrate a major, sex-linked, role for the CRF1 receptor in sociability deficits and related brain alterations induced by morphine, suggesting new therapeutic strategy for opiate use disorders.https://elifesciences.org/articles/100849CRF systemsociability deficitmorphineCRF1 receptorpharmacologygenetics |
| spellingShingle | Alessandro Piccin Anne-Emilie Allain Jérôme M Baufreton Sandrine S Bertrand Angelo Contarino Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice eLife CRF system sociability deficit morphine CRF1 receptor pharmacology genetics |
| title | Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice |
| title_full | Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice |
| title_fullStr | Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice |
| title_full_unstemmed | Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice |
| title_short | Disruption of the CRF1 receptor eliminates morphine-induced sociability deficits and firing of oxytocinergic neurons in male mice |
| title_sort | disruption of the crf1 receptor eliminates morphine induced sociability deficits and firing of oxytocinergic neurons in male mice |
| topic | CRF system sociability deficit morphine CRF1 receptor pharmacology genetics |
| url | https://elifesciences.org/articles/100849 |
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