Neonatal fluoxetine exposure alters motor performances of adolescent rats

Lee, Li-Jen; Lee, Lukas Jyuhn-Hsiarn

doi:10.1002/dneu.20942

Cited by 46 publications

(61 citation statements)

References 53 publications

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“…Neonatal exposure to SSRIs fluoxetine and citalopram increased adult offspring’s anxiety-like behavior in multiple tests (Ansorge et al, 2008). Likewise, perinatal exposure to the tricyclic clomipramine (Andersen et al, 2010) and the SSRI fluoxetine (Noorlander et al, 2008) increased anxiety in the EPM, although other groups found no effect of neonatal citalopram (Harris et al, 2012) fluoxetine (Lisboa et al, 2007, Lee and Lee, 2012), or escitalopram (Bourke et al, 2013b). Other work reported that early-life citalopram exposure enhanced adult locomotor activity (Maciag et al, 2006a, Maciag et al, 2006b), while others found the opposite effect (Ansorge et al, 2008, Noorlander et al, 2008, Lee and Lee, 2012).…”

Section: Discussionmentioning

confidence: 99%

Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats

et al. 2015

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Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10–20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children’s developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers’ anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively-bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring’s emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams’ pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7–21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.

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Section: Discussionmentioning

confidence: 99%

Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats

et al. 2015

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“…This loss of complexity in the somatosensory cortex may account for the deficits in tactile sensation described above. Similar decreases in either spine density or dendritic complexity have also been noted in pyramidal neurons in layer V of the motor cortex and medium spiny neurons in the striatum [41], though a rare increase in spine density was observed in hippocampal CA1 dendrites in adult mice following postnatal exposure [40]. …”

Section: Neuroanatomical Outcomesmentioning

confidence: 92%

“…In adolescence, early exposure inhibits locomotion [23,41,50,51] and decreases novel object exploration [52]. Lisboa et al [35] observed decreased locomotion only in male mice, suggesting a difference in sensitivity between the sexes.…”

Section: Long-term Behavioural Outcomesmentioning

confidence: 99%

“…Bairy et al [23] noted that male and female rats exposed prenatally to FLX performed better on a test of motor coordination in which the rat had to walk on a rotating cylinder. However, Lee and Lee [41] found that male adolescent rats briefly exposed to a higher dose of FLX during the early postnatal period were quicker to fall off the cylinder than controls, though this difference was abolished after several training sessions. Though these reports appear contradictory, it is possible that both are accurate; it could be the case that FLX is beneficial to motor coordination during the prenatal period but deleterious postnatally, or that FLX improves motor coordination at lower levels of exposure while impairing it at higher levels.…”

Section: Long-term Behavioural Outcomesmentioning

confidence: 99%

“…The bulk of the evidence indicates that FLX exposure either does not alter anxiety in adolescent or adult animals [23,35,37,39,40,41,42,43] or causes an increase [10,11,44,45,46]. Interestingly, it appears that the novelty-suppressed feeding/drinking tests are particularly sensitive to the effects of FLX exposure, as differences have been found in these tests without observing changes in the EPM or OFT [11,44,45].…”

Section: Long-term Behavioural Outcomesmentioning

confidence: 99%

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Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

2013

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During and following pregnancy, women are at high risk of experiencing depression, for which fluoxetine (FLX; brand names Prozac, Sarafem, Rapiflux) is the most commonly prescribed treatment. An estimated 1.4-2.1% of pregnant women use this medication, which inhibits the reuptake of serotonin and thereby increases serotonergic activity at the synapse. Serotonin acts as a cue guiding numerous neurodevelopmental processes, and changes in the concentration of serotonin can disrupt normal in utero brain development and organization in humans and other animals, thus providing a mechanism by which maternal intake of FLX might alter neural development and ultimately behaviour. Despite this possibility, long-term alterations of behaviour and the brain have not been well studied in individuals exposed to FLX during pregnancy or soon after birth, perhaps because conducting such studies beyond infancy presents significant challenges. To remedy this problem, many researchers have turned to modelling the effects of developmental FLX exposure in non-human animals, primarily rodents. The body of literature on this topic has expanded considerably over the past several years, yet a comprehensive review is lacking. In order to fill this gap, we have summarized the findings of those studies describing the long-term behavioural and neurophysiological effects of FLX exposure in non-human animals in early development. We also discuss methodological considerations and common shortcomings of research in this area. The precise nature of the long-term effects of developmental FLX exposure remains difficult to specify, as these effects appear to be highly variable and dependent on numerous factors. Overall, however, it is clear that early FLX exposure in non-human animals can alter the development of the brain in ways that are relevant to behaviour in adulthood, decreasing exploration and social interaction, and in some cases altering anxiety- and depression-like behaviours.

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

Zimmerberg

Germeyan

2014

Developmental Psychobiology

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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.

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Neonatal fluoxetine exposure alters motor performances of adolescent rats

Cited by 46 publications

References 53 publications

Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats

Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

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

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