Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alc
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ORIGINAL INVESTIGATION
Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alcohol intake in female mice Fabio Bellia 1 & Andrea Suarez 2 & Claudio D’Addario 1,3 & Ricardo Marcos Pautassi 2,4 & María Carolina Fabio 2,4 Received: 29 June 2020 / Accepted: 21 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, including altered anxiety response and problematic use of alcohol. Objective we analyzed, in mice, the effects of transient 5-HT depletion at infancy or adolescence on subsequent anxiety-like behavior and alcohol intake during adolescence. Methods C57/BL6 male and female mice were administered a 5-HT synthesis inhibitor (PCPA; 4-chloro-DL-phenylalanine methyl ester hydrochloride) at infancy (postnatal days 14–16 [PD14–16]) or adolescence (PD40–42). Eleven (± 1) days after treatment, mice were assessed for ethanol intake in daily two-bottle choice tests and for anxiety response via the elevated plus maze. Results Female, but not male, mice transiently depleted of 5-HT at adolescence (but not those depleted at the perinatal stage) exhibited a significant reduction in anxiety response, which was accompanied by a significant reduction on alcohol intake. Conclusion Transient 5-HT inhibition at adolescence may act, in females, as a protective factor for the emergence of anxiety disorders and problematic use of alcohol during adolescence. Keywords 5-HT . PCPA . Sensitive periods . Adolescence . Infancy . Anxiety behavior . EPM . Alcohol
Introduction Serotonin (5-HT) is a monoamine neuromodulator involved in the formation of brain circuits, in the regulation of mood and anxiety, and in the development of addiction (Bonnin and Levitt 2011; Velasquez et al. 2013; Lin et al. 2014; Olivier 2015). It has been reported that 5-HT 1A receptors (5-HT1A) of the bed nucleus of the stria terminalis buffer anxiety reactions (Marcinkiewcz et al. 2019) and, more recently, that 5* María Carolina Fabio [email protected] 1
Università degli Studi di Teramo, Teramo, Italy
2
Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC), Cordoba, Argentina
3
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
4
Facultad de Psicología, Universidad Nacional de Córdoba , Cordoba, Argentina
HT pathways in the medial (MRN) and dorsal raphe nuclei (DRN) regulate anxiety-like and mood behaviors, respectively (Ohmura et al. 2019). Anxiety disorders have developmental origins, involving 5-HT. For example, alterations of 5-HT1A hetero-receptors in the prefrontal cortex at adolescence, but not at adulthood, result in lifelong increases in conflict-bas
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