Increased Aggression, Improved Spatial Memory, and Reduced Anxiety-Like Behaviour in Adult Male Mice Exposed to Fluoxetine Early in Life

Abstract

Rationale: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory. Objectives: To further delineate the long-term behavioural effects of altering 5-HT during development, we examined the effects of perinatal Flx exposure on the behaviour of male mice as adults. Methods: Dams were treated with approximately 25 mg/kg/day of Flx from embryonic day 15 to postnatal day 12, and the behaviour of the adult offspring was assessed. Results: We found that perinatal Flx exposure leads to increased aggression, improved spatial memory, and reduced anxiety-like behaviour. This exposure did not cause memory deficits, changes in sensory processing, or changes in gross motor function. Conclusions: Our results suggest that while perinatal exposure to Flx may have long-term effects on adult behaviour, these effects appear limited and not necessarily detrimental.

Prenatal exposure to selective serotonin reuptake inhibitors (SSRI) increases aggression and modulates maternal behavior in offspring mice

“…Lisboa et al () reported that exposure to FLX during pregnancy and lactation had no effect on the number and duration of aggressive attacks in mice. In contrast, Kiryanova and Dyck () reported that exposure of mouse dams to high dose of FLX beginning on gestation Day 15 until postnatal Day 12 increased aggression of male mouse offspring. Along the same lines, it was shown that exposure to fluoxetine on gestation days 13–21 increased foot shock‐induced aggression in male offspring (Singh, Jaiswal, Singh, & Bhattacharya, ).…”

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

“…These lower doses of fluoxetine may not be sufficient to alter offspring development, or there may be differences in offspring outcome if dams are treated with fluoxetine throughout gestation as well as postpartum. Furthermore, higher doses of maternal fluoxetine (25 mg/kg/day) during mid-gestation (prenatal day 15) through postpartum (postnatal day 12) decreased anxiety-like behavior in adult male (Kiryanova and Dyck, 2014) and female mice (McAllister et al, 2012). Together, this highlights the importance of dose and timing of fluoxetine as crucial methodological factors when evaluating effects of maternal fluoxetine on offspring outcome (reviewed in Kiryanova et al, 2013).…”

Perinatal fluoxetine has enduring sexually differentiated effects on neurobehavioral outcomes related to social behaviors

“…For example, pre-gestational stress can affect the developing 5HT system as well as HPA axis reactivity in rat offspring (Gemmel et al, 2017;Gemmel et al, 2018c;Huang et al, 2013;Huang et al, 2010;Huang et al, 2012). Expanding on previous work we expected that pSSRIs would increase social interactions in female offspring, while pre-gestational maternal stress would decrease social behaviors in male offspring, with the exception of social play (pouncing/nape attacks) which has been linked to serotonin levels (Kepser and Homberg, 2015;Kiryanova and Dyck, 2014). We predicted that pSSRIinduced effects on social interactions would be related to alterations in the HPA system as well as the…”