Perinatal citalopram does not prevent the effect of prenatal stress on anxiety, depressive‐like behaviour and serotonergic transmission in adult rat offspring

Abstract

It is still not clear whether the selective serotonin reuptake inhibitors frequently prescribed to depressed pregnant women improve the behavioural outcome in their children. The current study investigated whether administration of citalopram to pregnant rats could prevent anxiety and depressive-like behaviour induced by gestational stress in their offspring, and restore the expression of serotonin 1A autoreceptors in GABAergic interneurons in the medial prefrontal cortex and dorsal raphe nuclei in males, and of corticotropin-releasing factor type 2 receptors in GABAergic interneurons in the dorsal raphe nuclei in females. Activation of these receptors modulates serotonergic transmission to target areas and is reduced in a sex-dependent manner by prenatal stress. Citalopram (10 mg/kg/day), administered orally from day 7 of gestation until 21 days postpartum, prevented the increase in anxiety in stressed mothers but did not reduce anxiety and depressive-like behaviour in their offspring and even induced depressive-like behaviour in the offspring of control mothers. Citalopram failed to restore the reduction in the expression of serotonin 1A autoreceptors in the prefrontal cortex of males and in corticotropin-releasing factor type 2 receptors in the dorsal raphe nuclei of females induced by prenatal stress. Prenatal citalopram did not prevent the behavioural changes or reduction in serotonergic transmission to target areas induced by prenatal stress. It had adverse behavioural effects in the offspring of control rats, which, together with the lack of any change in prenatally-stressed rats, may be due to inhibition of the foetal serotonin transporter thereby preventing normal development of the serotonin system.

Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open‐field activity in Sprague‐Dawley rats

“…Route of exposure may also influence outcomes among these studies. For example, CIT treatment in Wistar dams (via drinking water) from E7 to P21 increased behavioral despair of offspring in the FST (Zohar et al, 2016); this route may have resulted in steady levels of CIT compared with the present study's use of twice daily s.c. injections that likely would produce oscillating CIT levels and thus episodic periods of SERT inhibition (Ansorge et al, 2008). Other studies report no effects on depression‐like behavior (Coleman et al, 1999; Olivier et al, 2011b; Rayen et al, 2011), and some have even found decreased forced swim despair (Karpova et al, 2009; Mendes‐da‐Silva et al, 2002) after developmental SSRI administration (i.p.…”

“…Anxiety is often seen in ASD (Gillott et al, 2001; MacNeil et al, 2009; Olexová et al, 2016), and developmental exposure to SSRIs in rodents leads to increased anxiety‐like behavior (Ansorge et al, 2008, 2004; Bairy et al, 2007; Karpova et al, 2009; Noorlander et al, 2008; Olivier et al, 2011b; Sarkar et al, 2014; Soga et al, 2012; Zohar et al, 2016). We showed that perinatal exposure to 10 mg/kg CIT increased anxiety in open‐field and marble burying (Sprowles et al, 2016).…”

“…ASD children have impaired social interactions (MacNeil et al, 2009; Olexová et al, 2016), and studies report decreased social preference and/or increased depressive‐like behavior in rodents developmentally exposed to SSRIs (Ansorge et al, 2004; Boulle et al, 2016; Glover et al, 2015; Olivier et al, 2011b; Rebello et al, 2014; Rodriguez‐Porcel et al, 2011; Sarkar et al, 2014; Zohar et al, 2016). We showed that perinatal exposure to 10 mg/kg CIT increased behavioral despair in the FST but did not affect social preference (Sprowles et al, 2016).…”

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague‐Dawley rats

“…It has also been demonstrated that neonatal exposure to clomipramine (a tricyclic AD) in rats resulted in increased anxiety on the EPM and marble burying (Andersen et al, 2010). And most recently, rats perinatally exposed to Cit displayed increased anxiety on the EPM and increased immobility in the FST (Zohar et al, 2016). Note that these changes are consistent across studies despite using different SSRIs (Glover et al, 2015).…”

The adaptive brain in mental health: overcoming inherited risk factors

“…In animal studies, the effects of treatment of mothers during gestation may also result in anxiety or depression in the offspring 31 or may lack efficacy. 32 Treatment of breast-feeding women during the early postpartum period may result in 20% antidepressant transfer through the milk, but is considered a relatively safe option. 33,34 However, there is some evidence of behavioural or psychomotor impairment in human infants following prenatal exposure to SSRIs, but further study is needed.…”