Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam

Pawluski, Jodi L.; Charlier, Thierry; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda; Steinbusch, Harry W.M.; Hove, Daniël L.A. van den

doi:10.1016/j.bbr.2011.11.043

Cited by 85 publications

(89 citation statements)

References 74 publications

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“…First, maternal behaviour was assessed only with one test (pup retrieval). While we and a number of other researchers [73,86,89,90] have not found differences in maternal behaviour between Flx-exposed and control dams, Pawluski et al [91] demonstrated an increase in arched-back nursing in rat dams exposed to Flx. Because maternal behaviour is known to affect offspring outcomes, a more thorough investigation following Flx administration is crucial.…”

Section: Discussioncontrasting

confidence: 70%

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

Kiryanova

Dyck

2014

Dev Neurosci

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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.

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Section: Discussioncontrasting

confidence: 70%

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

Kiryanova

Dyck

2014

Dev Neurosci

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“…The dentate gyrus and CA3 region of the hippocampus was additionally assessed for synaptophysin density to investigate aspects of synaptic plasticity. Every 12th section throughout the hippocampus was stained as previously described (Pawluski et al , 2012bRayen et al 2011). …”

Section: Methodsmentioning

confidence: 99%

Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

et al. 2014

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“…Capello et al [42] identified the dosage of FLX that produces serum levels in rat dams that are similar to the levels observed in pregnant women. Other studies have also attempted to mimic the FLX levels of post-partum women in dams [65,70]. Though this represents a good start, more studies should take similar steps.…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…Though seldom examined, it does indeed appear that FLX treatment can alter the behaviour of rat dams. It has been reported to increase the amount of licking and grooming the dam performs on the pups [76] as well as the incidence of nursing from the arched-back posture [70], in which the dam is more active and engages in more licking/grooming. This is an important finding, as increases in licking/grooming and arched-back nursing are associated with long-term decreases in the physiological response to stress, as well as decreases in anxiety-related behaviours [for a review, see [77].…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…Thus, there exists a mechanism by which maternal FLX treatment may confound examination of the direct effects of FLX exposure on the offspring. However, other studies have shown that maternal FLX treatment does not alter the total time dams spend licking/grooming or nursing the offspring [38,65,70], suggesting that if FLX treatment does affect maternal behaviour in rat dams, it does so subtly, and perhaps in a way that privileges very specific behaviours. If this is the case, then it may not be recommendable for studies to include cursory examinations of maternal behaviour, as such examinations may give the impression that maternal behaviour is not altered when in fact they lack the specificity to detect the relevant effects.…”

Section: Methodological Considerationsmentioning

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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Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam

Cited by 85 publications

References 74 publications

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

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

Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

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

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