Neonatal Fluoxetine Exposure Affects the Neuronal Structure in the Somatosensory Cortex and Somatosensory-Related Behaviors in Adolescent Rats

Abstract

Selective serotonin reuptake inhibitor (SSRI)-type antidepressants are often prescribed to depressive pregnant women for their less adverse side effects. However, growing evidences have shown increased congenital malformations and poor neonatal adaptation in the perinatal SSRI-exposed human infants as well as animal pups. In this study, we examined the effects of early exposure of fluoxetine, the most popular SSRI-type antidepressant, on the developing somatosensory system. Physiological saline or fluoxetine (10 mg/kg) was subcutaneously injected into neonatal rats from P0 to P6. Somatosensory-related behaviors were examined in adolescence (P30-P35). Morphological features of the primary somatosensory cortex were checked at P7 and P35. The tactile and thermal perceptions as well as locomotor activity were affected by neonatal fluoxetine treatment. At the morphological level, the number of branch tips of thalamocortical afferents to the somatosensory cortex was reduced in the fluoxetine-treated rats. Furthermore, the spiny stellate neurons in the layer IV somatosensory cortex had reduced dendritic span and complexity with fewer branches, shorter dendritic length, and smaller dendritic field. The spine density of spiny stellate neurons was significantly reduced whereas the spine length of mushroom- and branched-type was increased. Taken together, these results indicate that neonatal fluoxetine administration has long-lasting effects on the function and structure in the somatosensory system. Sensory information processing may be disturbed in the neonatal fluoxetine-treated animals due to the structural deformation in the thalamocortical afferents and dendritic structures of the spiny stellate neurons in the layer IV somatosensory cortex.

Prenatal exposure to antidepressants and language competence at age three: results from a large population‐based pregnancy cohort in Norway

“…24 SSRI treatments in early life in rats have been shown to have long-lasting effects on both the structure and the function of the somatosensory system. 25,26 It is not known whether these effects of SSRIs are paralleled in humans, but the findings may indicate that there is a biological explanation for the main finding of our study.…”

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

“…Further, SSRI exposure was associated with decreased activity in juvenile [134] (for review see 135) and increased activity adult offspring [14]. In line with this, 5-HTT knockout rats, which exhibit high levels of 5HT, also show reduced motor activity late in adulthood, but this effect is only evident in male and not female rats [10].…”

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

“…The relevance of these findings needs to be explored further in vivo to determine how SSRIs affect plasticity and development of the cerebellum . However, prenatal SSRI exposure has been associated with deficits in postnatal motor control in rodent species as well as human infants [47,48,49,50] and it is likely that alterations in motor control may be due, in part, to the effect of prenatal SSRI exposure on cerebellar development.…”