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Combination of Gestational Sub‐Therapeutic Prozac with Tryptophan Depletion Sex Dependently Worsens Social Behavior in Adolescence
Author(s) -
Garbarino Valentina Rose,
Edwards Marshall Thomas,
Gutierrez Ednia,
Santos Taylor,
Javors Martin,
Daws Lynette C.,
Gould Georgianna Grimshaw
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.989.11
Subject(s) - fluoxetine , offspring , psychology , autism , antidepressant , serotonin , serotonin reuptake inhibitor , reuptake inhibitor , pregnancy , serotonin transporter , behavioural despair test , endocrinology , medicine , psychiatry , pharmacology , anxiety , biology , receptor , genetics
Depression is a serious mood disorder that can require antidepressant use during pregnancy. Safety concerns have been raised about the effects of selective‐serotonin reuptake inhibiting (SSRI) antidepressants on fetal brain development. One of the most common SSRIs prescribed during pregnancy is fluoxetine (Prozac). Fluoxetine blocks serotonin (5‐HT) reuptake by the 5‐HT transporter (SERT). 5‐HT is vital for shaping neural circuitry during development, and aberrant fetal 5‐HT levels can increase the risk of autism risk, which is diagnosed with the presence of social behavior deficits and repetitive behaviors. Placental transfer studies show fetal 5‐HT availability may be highly dependent upon maternal availability of its precursor, tryptophan (TRP). Hence, elucidation of the relationship between maternal and fetal TRP and 5‐HT demand and availability is crucial to understanding their role in autism susceptibility. Using a mouse model of maternal SSRI exposure with dietary TRP manipulations during pregnancy, we measured the social interaction and social novelty preference (3 Chamber Test for Social Interaction and Novelty Preference), as well as the repetitive behavior (Marble Burying Test) of adolescent offspring. We hypothesized a daily sub‐therapeutic dose (1 mg/kg/day) of fluoxetine, would impair offspring sociability with relevance to autistic behaviors. In prior studies higher fluoxetine doses increased 5‐HT turnover. Hence we predicted that if a low dose SSRI was combined with dietary TRP deficiency, offspring could develop persistent sociability deficits. Our preliminary findings partially support this hypothesis, as either prenatal fluoxetine exposure or TRP depletion alone, or in combination, impaired sociability preference, in a sex dependent and sociability test phase dependent manner. Treated males seem to lose interaction preference, spending less time with a social interaction stimulus, but maintain normal preference for social novelty based on dwelling time in chambers. Females differentially demonstrate normal social interaction preference, but show a loss of preference for social novelty with fluoxetine treatment in measures of time spent in chamber and time sniffing social or novel stimuli. Additionally, in a measure of repetitive behavior, females exposed to TRP depletion or the combined treatment buried more marbles than males. Our early results suggest that females may be more sensitive to in utero exposure to 5‐HT altering factors, and that males and females may compensate for their developmentally altering effects by different mechanisms. Support or Funding Information Research supported by NICHD: HD081261. V. Garbarino is supported by a Biology of Aging Training Grant: T32 AG021890.