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dc.contributor.author
Fabio, Maria Carolina
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dc.contributor.author
Servin Bernal, Ivan Julio Cesar
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dc.contributor.author
Degano, Alicia Laura
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dc.contributor.author
Pautassi, Ricardo Marcos
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dc.date.available
2023-08-14T16:51:30Z
dc.date.issued
2022-09-05
dc.identifier.citation
Fabio, Maria Carolina; Servin Bernal, Ivan Julio Cesar; Degano, Alicia Laura; Pautassi, Ricardo Marcos; Serotonin disruption at gestation alters expression of genes associated with serotonin synthesis and reuptake at weaning; Springer; Psychopharmacology; 239; 10; 05-9-2022; 3355-3366
dc.identifier.issn
0033-3158
dc.identifier.uri
http://hdl.handle.net/11336/208185
dc.description.abstract
Rationale: Serotonin (5-HT) is a monoamine neuromodulator that plays a key role in the organization of the central nervous system. 5-HT alterations may be associated to the emergence of social deficits and psychiatric disorders, including anxiety, depression, and substance abuse disorders. Notably, disruption of the 5-HT system during sensitive periods of development seems to exert long-term consequences, including altered anxiety responses and problematic use of alcohol. Objective: We analyzed, in mice, the effects of transient 5-HT depletion at gestation (a developmental stage when medial prefrontal cortex (mPFC) 5-HT levels depend exclusively on placental 5-HT availability) on 5-HT central synthesis and reuptake at weaning. We also explored if 5-HT disruption at the embryonic stage influences behavioral outcomes that may serve as a proxy for autistic- or anxiety-like phenotypes. Methods: C57/BL6 male and female mice, born from dams treated with a 5-HT synthesis inhibitor (PCPA; 4-Chloro-DL-phenylalanine methyl ester hydrochloride) at gestational days (G)13.5–16.5, were subjected to a behavioral battery that assesses social preference and novelty, compulsive behavior, stereotypies, and ethanol’s anti-anxiety effects, at postnatal days (P) 21–28. Afterwards, expression of the genes that encode for 5-HT synthesis (Tph2) and SERT (5-HT transporter) were analyzed in mPFC via real-time RT-PCR. Dopamine 2 receptor (D2R) expression was also analyzed via RT-PCR to further explore possible effects of PCPA on dopaminergic transmission. Results: Transient 5-HT disruption at G13.5–16.5 reduced Tph2 expression of both male and female mice in mPFC at P23. Notably, female mice also exhibited higher SERT expression and reduced D2R expression in mPFC. Mice derived from 5-HT depleted dams displayed heightened compulsive behavior at P21, when compared to control mice. Alcohol anti-anxiety effects at early adolescence (P28) were exhibited by mice derived from 5-HT depleted dams, but not by control counterparts. No social deficits or stereotyped behaviors were observed. Conclusion: Transient 5-HT inhibition at gestation resulted in altered expression of genes involved in 5-HT synthesis and reuptake in mPFC at weaning, a period in which the 5-HT system is still developing. These alterations may exert lingering effects, which translate to significant compulsivity and heightened sensitivity to the anxiolytic effects of alcohol at early adolescence.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
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dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
5-HT
dc.subject
ALCOHOL
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COMPULSIVE BEHAVIOR
dc.subject
EMBRYONIC STAGE
dc.subject
EPM
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PCPA
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TPH2-SERT
dc.subject.classification
Otros Tópicos Biológicos
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Serotonin disruption at gestation alters expression of genes associated with serotonin synthesis and reuptake at weaning
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-04T10:55:27Z
dc.identifier.eissn
1432-2072
dc.journal.volume
239
dc.journal.number
10
dc.journal.pagination
3355-3366
dc.journal.pais
Alemania
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dc.description.fil
Fil: Fabio, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina
dc.description.fil
Fil: Servin Bernal, Ivan Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
dc.description.fil
Fil: Degano, Alicia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Pautassi, Ricardo Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina
dc.journal.title
Psychopharmacology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/10.1007/s00213-022-06228-z
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00213-022-06228-z
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