Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats
Abstract Mood disorders, including anxiety and depression caused by prenatal ethanol exposure (PE) are prevalent conditions in fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is associated with persistent dysfunctions of several neurotransmitter systems, including the serotonin (...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02210-7 |
| _version_ | 1811182309773148160 |
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| author | Saida Oubraim Ruixiang Wang Kathryn Hausknecht Martin Kaczocha Roh-Yu Shen Samir Haj-Dahmane |
| author_facet | Saida Oubraim Ruixiang Wang Kathryn Hausknecht Martin Kaczocha Roh-Yu Shen Samir Haj-Dahmane |
| author_sort | Saida Oubraim |
| collection | DOAJ |
| description | Abstract Mood disorders, including anxiety and depression caused by prenatal ethanol exposure (PE) are prevalent conditions in fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is associated with persistent dysfunctions of several neurotransmitter systems, including the serotonin (5-HT) system, which plays a major role in mood regulation and stress homeostasis. While PE is known to disrupt the development of the 5-HT system, the cellular mechanisms by which it alters the function of dorsal raphe nucleus (DRn) 5-HT neurons and their synaptic inputs remain unknown. Here, we used a second-trimester binge-drinking pattern PE (two daily gavages of 15% w/v ethanol at 3 g/kg, 5–6 h apart) during gestational days 8 - 20 and measured anxiety-like behaviors of adult male rats using the elevated plus (EPM) and zero (ZM) mazes. We also employed ex-vivo electrophysiological and pharmacological approaches to unravel the mechanisms by which PE alters the excitability and synaptic transmission onto DRn 5-HT neurons. We found that PE enhanced anxiety-like behaviors in adult male rats and induced a persistent activation of DRn 5-HT neurons. The PE-induced activation of DRn 5-HT neurons was largely mediated by potentiation of DRn glutamate synapses, which was caused by activation of the nitrergic system and impaired endocannabinoid signaling. As such, the present study reveals “push-pull” effects of PE on nitrergic and eCB signaling, respectively, which mediate the enhanced activity of DRn 5-HT neurons and could contribute to anxiety-like behaviors observed in animal model of FASD. |
| first_indexed | 2024-04-11T09:30:35Z |
| format | Article |
| id | doaj.art-c26d064334a9484bb011af6fcda1e12e |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-11T09:30:35Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-c26d064334a9484bb011af6fcda1e12e2022-12-22T04:31:55ZengNature Publishing GroupTranslational Psychiatry2158-31882022-10-0112111210.1038/s41398-022-02210-7Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male ratsSaida Oubraim0Ruixiang Wang1Kathryn Hausknecht2Martin Kaczocha3Roh-Yu Shen4Samir Haj-Dahmane5Department of Pharmacology and Toxicology, State University of New YorkDepartment of Pharmacology and Toxicology, State University of New YorkDepartment of Pharmacology and Toxicology, State University of New YorkDepartment of Anesthesiology, Stony Brook UniversityDepartment of Pharmacology and Toxicology, State University of New YorkDepartment of Pharmacology and Toxicology, State University of New YorkAbstract Mood disorders, including anxiety and depression caused by prenatal ethanol exposure (PE) are prevalent conditions in fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is associated with persistent dysfunctions of several neurotransmitter systems, including the serotonin (5-HT) system, which plays a major role in mood regulation and stress homeostasis. While PE is known to disrupt the development of the 5-HT system, the cellular mechanisms by which it alters the function of dorsal raphe nucleus (DRn) 5-HT neurons and their synaptic inputs remain unknown. Here, we used a second-trimester binge-drinking pattern PE (two daily gavages of 15% w/v ethanol at 3 g/kg, 5–6 h apart) during gestational days 8 - 20 and measured anxiety-like behaviors of adult male rats using the elevated plus (EPM) and zero (ZM) mazes. We also employed ex-vivo electrophysiological and pharmacological approaches to unravel the mechanisms by which PE alters the excitability and synaptic transmission onto DRn 5-HT neurons. We found that PE enhanced anxiety-like behaviors in adult male rats and induced a persistent activation of DRn 5-HT neurons. The PE-induced activation of DRn 5-HT neurons was largely mediated by potentiation of DRn glutamate synapses, which was caused by activation of the nitrergic system and impaired endocannabinoid signaling. As such, the present study reveals “push-pull” effects of PE on nitrergic and eCB signaling, respectively, which mediate the enhanced activity of DRn 5-HT neurons and could contribute to anxiety-like behaviors observed in animal model of FASD.https://doi.org/10.1038/s41398-022-02210-7 |
| spellingShingle | Saida Oubraim Ruixiang Wang Kathryn Hausknecht Martin Kaczocha Roh-Yu Shen Samir Haj-Dahmane Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats Translational Psychiatry |
| title | Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| title_full | Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| title_fullStr | Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| title_full_unstemmed | Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| title_short | Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| title_sort | prenatal ethanol exposure causes anxiety like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats |
| url | https://doi.org/10.1038/s41398-022-02210-7 |
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