Effects of neonatal fluoxetine exposure on behavior across development in rats selectively bred for an infantile affective trait

Abstract

Infants born to women with depressive symptoms are at higher risk for insecure attachment and behavioral problems. Thus current medical practice is to continue psychotropic medication of pregnant women with depression despite concerns about its behavioral teratology. There are few animal studies focused on long-term behavioral effects of prenatal antidepressant exposure; in addition, studies have not looked at individual differences in baseline affective state as a source of response variability. In this study, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was administered to male and female rat pups from postnatal days 2-7 to model exposure to antidepressants in the human third trimester. Four behavioral measures were conducted from the neonatal to adult age periods in Low and High lines selectively bred for their rate of ultrasonic vocalizations after brief maternal separation. Neonatal fluoxetine administration decreased distress calls in both lines, but to a greater extent in High line rats than Low line. Neonatal fluoxetine also impaired motor coordination in neonates. Neonatal fluoxetine administration decreased social behavior in both juvenile and adult subjects. Fluoxetine-related reductions in anxiety behavior were not observed at the two older ages. As expected, High line subjects displayed more anxiety behavior than Low line subjects at all three test ages. These results suggest that there are may be significant behavioral consequences of antidepressant use during late pregnancy on offspring maternal attachment and social behavior, with implications for increased risk of autism spectrum disorders.

Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies

“…Animal models converge with evidence from human studies as early exposure to SSRIs results in delayed motor abilities in pre-weaning offspring and juvenile offspring [131][132][133].…”

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…At such concentrations, a mixture of fluoxetine, carbamazepine and venlafaxine, or valproate produce expression changes in genes related to neuronal growth, development and regulation, and to autism in SK-N-SH neuroblastoma cells [122]. Neonatal fluoxetine administration in rats impairs motor coordination in neonates and decreased social behaviour in both juvenile and adult offspring [123] Terbutaline β2-adrenergic receptor agonist, used as a tocolytic (anticontraction medication) to delay preterm labour for up to 48 hours Terbutaline exposure for >2 days during the third trimester associated with a fourfold increased risk for autism spectrum disorders (not observed with albuterol) [124] In rats, maternal stress during pregnancy, or terbutaline administration to the neonates, on postnatal days 2-5 resulted in autistic-like behaviour in the offspring (stereotyped/repetitive behaviour and deficits in social interaction or communication [125]. Newborn rats treated with terbutaline (10 mg/kg) daily on postnatal days 2 to 5 or PN 11 to 14 showed a robust increase in microglial activation on postnatal day 30 in the cerebral cortex, as well and in cerebellar and cerebrocortical white matter.…”

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

“…Some studies have indicated that developmental SSRI exposure decreases social interaction in either male offspring [25,27] or female offspring [31], while others found an increase in sniffing behavior towards conspecifics [32,33]. When looking at the motivation for social interaction in particular, the majority found that SSRI exposure negatively affects the motivation to start social contact [26,28,29,34]. The inconsistent results make it impossible to draw conclusions about the risk for long-term affected social behavior in the offspring.…”