Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alcohol intake in female mice

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.