Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice

Kummet, Gary J.; Haskell, Sarah E.; Hermann, Gregory M.; Ni, Charles; Volk, Kenneth A.; Younes, Areej K.; Miller, Alise K.; Roghair, Robert D.

doi:10.1155/2012/431574

Cited by 15 publications

(17 citation statements)

References 52 publications

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“…weaning but not at adulthood (5-7 months); however, upon necropsy, both SSRI exposed female (11-12 months) and male mice (6-9 months) had reduced weight than controls [94].…”

Section: Animal Studiesmentioning

confidence: 93%

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

Hutchison

Mâsse

Pawluski

et al. 2018

Reproductive Toxicology

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. Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond A review of animal and human studies. Reproductive Toxicology, Elsevier, 2018, 77, pp.109-121. 10 Highlights  Our paper reviews our current understanding of the impact of prenatal SSRI exposure on weight and growth using both human and animal findings.  Our review extends the previously published review paper by Grzeskowiak and colleagues in Repro Tox in 2012 by including findings beyond infancy, the impact of maternal mood -pre and post natal, and given that the majority our 5HT is in the gastrointestinal (GI) system we speculate that altering 5HT signaling, via SSRI exposure might have an impact on GI function and later weight gain.  With recent advances in our understanding of the gut-brain axis and the role of 5HT, we raise critical questions about how weight and growth outcomes might be related to SSRI induced changes in the GI microbiome.  Our paper provides an updated review of the literature (e.g., Leuner et al 2014;Nezvalová-Henriksen et al., 2016), with a particular focus on weight related outcomes beyond birth, developmental aspects of SSRI exposure that might also impact weight and growth, as well as provides detailed suggestions for future research. AbstractThe long-term impact of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment during pregnancy and postpartum on offspring outcomes is still not clear. Specifically, perinatal SSRI exposure may have long-term consequences for body weight and related health outcomes in the newborn period and beyond. This review focuses on the impact of perinatal SSRI exposure on weight using human and animal findings. The impact of maternal mood is also explored. We propose potential mechanisms for weight changes, including how early alterations in serotonin signaling may have implications for weight via changes in metabolism and motor development.As the majority of serotonin is in the gastrointestinal (GI) system we also speculate that perinatal SSRI exposure might alter the brain-gut relationship, via the microbiome, leading to changes in feeding behavior and weight.

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“…weaning but not at adulthood (5-7 months); however, upon necropsy, both SSRI exposed female (11-12 months) and male mice (6-9 months) had reduced weight than controls [94].…”

Section: Animal Studiesmentioning

confidence: 93%

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

Hutchison

Mâsse

Pawluski

et al. 2018

Reproductive Toxicology

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“…25–27 In addition to behavioral phenotypes consistent with rebound depression, we have shown SSRI-exposed mice have reduced left ventricular volumes and a programmed hypermetabolic state. 27,28 We further demonstrated that mice exposed to neonatal sertraline have increased adult heart rates, increased very low frequency heart rate variability, and increased urinary excretion of noradrenaline, together suggesting increased sympathetic tone. 27 Because impaired cardiac remodeling and increased sympathetic tone correlates with increased post-MI morbidity and mortality, we hypothesized that neonatal SSRI exposed mice will have increased mortality following myocardial infarction in adulthood.…”

Section: Introductionmentioning

confidence: 58%

“…The sertraline dose was chosen to reflect exposure under the assumption that maternal therapy is prescribed at the lowest effective dose (50 to 100 mg/day). 28 This dose conversion accounted for differences in body surface area, 70% oral bioavailability, and 29% placental transfer efficiency and the approximation was validated by serum sampling, as detailed in our initial publication. 28 Pups were observed daily during injections.…”

Section: Methodsmentioning

confidence: 99%

“…28 This dose conversion accounted for differences in body surface area, 70% oral bioavailability, and 29% placental transfer efficiency and the approximation was validated by serum sampling, as detailed in our initial publication. 28 Pups were observed daily during injections. Sertraline-exposed and control pups were nursed by the same mother to minimize environmental influences on growth and development.…”

Section: Methodsmentioning

confidence: 99%

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Impact of Neonatal Sertraline Exposure on the Post–Myocardial Infarction Outcomes of Adult Male Mice

Haskell

Peotta²,

Reinking³

et al. 2013

Journal of Cardiovascular Pharmacology

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Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction morbidity and mortality. C57BL/6 mice received saline or sertraline (5 mg/kg IP) on post-natal days 1–14. At 5 months, male mice underwent coronary artery ligation and were monitored by radiotelemetry until death or 4 weeks post-ligation. Following ligation, SSRI exposed mice had increased heart rates (SSRI 516 ± 13 bpm, control 470 ± 15 bpm, p<0.05). SSRI-exposed mice had significant reductions in left ventricular systolic volumes both before and after coronary ligation (SSRI: baseline 20 ± 3 µL, post-MI 37 ± 10 µL; control: baseline 30 ± 3 µL, post-MI 65 ± 23 µL). Post-MI echocardiography showed significantly decreased ejection fraction in control mice (baseline 60 ± 4%, post-MI 41 ± 2%, p <0.01) but not SSRI-exposed mice (baseline 65 ± 3%, post-MI 53 ± 7%). Neonatal SSRI exposure did not significantly alter post-MI survival. We conclude that the preexisting SSRI-induced small left heart syndrome may provide protection from post-MI ventricular dilation.

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“…To assess the potential protective effect of ovarian function, bilateral ovariectomy (OVX) was completed at 4 months (control 17.7+/−2.2 wk; GR 17.6+/−2.3 wk). Post-ovariectomy data were collected an additional 4 to 6 weeks after the ovariectomies were performed (15). Analgesia during OVX included flunixin meglumine (2.5 mg/kg, subcutaneously once or twice daily for 48h with the first dose given at the time of isoflurane induction) and 0.5% bupivacaine applied to the wound margin.…”

Section: Methodsmentioning

confidence: 99%

Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice

et al. 2016

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Perinatal growth restriction is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal growth restriction (GR) programs hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy estrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the 10th percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-ovariectomy (OVX), and post-OVX with oral estrogen replacement. OVX elicited hypertension in GR mice that was significantly exacerbated by psychomotor arousal (systolic blood pressure at light to dark transition: control 122+/−2; GR 119+/−2; control-OVX 116+/−3; GR-OVX 126+/−3 mmHg). Estrogen partially normalized the rising blood pressure surge seen in GR-OVX mice (23+/−7% reduction). GR mice had left ventricular hypertrophy, and GR-OVX mice in particular had exaggerated bradycardic responses to sympathetic blockade. For GR mice, a baseline increase in baroreceptor reflex sensitivity and high frequency spectral power support a vagal compensatory mechanism, and that compensation was lost following OVX. For GR mice, the OVX-induced parasympathetic withdrawal was partially restored by estrogen (40+/−25% increase in high frequency spectral power, P<0.05). In conclusion, GR alters cardiac morphology and cardiovascular regulation. The hemodynamic consequences of GR are attenuated in ovarian-sufficient or estrogen replete females. Further investigations are needed to define the role of hormone replacement therapy targeted towards young women with estrogen deficiency and additional cardiovascular risk factors, including perinatal growth restriction, cardiac hypertrophy and morning surge hypertension.

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Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice

Cited by 15 publications

References 52 publications

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

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

Impact of Neonatal Sertraline Exposure on the Post–Myocardial Infarction Outcomes of Adult Male Mice

Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice

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