Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake

Pinheiro, Isabeli Lins; Silva, Aline Isabel da; Reginato, Andressa; Silva-Filho, Reginaldo; Galindo, Lígia Cristina Monteiro; Matos, Rhowena Jane Barbosa de; Ferraz, João Carlos; Toscano, Ana Elisa; Ferreira, Marciane Milanski; Castro, Raul Manhães de; Souza, Sandra Lopes de

doi:10.1016/j.bbr.2017.07.038

Cited by 15 publications

(9 citation statements)

References 43 publications

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“…The serotonin system consists of 15 different receptors that are key players at crucial neurodevelopmental stages, regulating neurogenesis, apoptosis, axon branching and dendritogenesis 11 . Many of the studies included in the synthesis of evidence in the current review, which have been selected on the presence of behavioral outcomes, also include outcomes reflecting brain health from the global to the molecular level: the corticosterone response to stress 74, 81, 96, 100, 123, 124, 126, 130, 135 , brain structure and connectivity 71, 77, 84, 93, 101, 110, 122 , neuronal health 59, 82, 85, 89, 104, 109, 111, 126, 135 , monoamine concentrations in the brain 43, 44, 46, 59, 105, 116, 117, 133, 135, 140, 141 , protein expression in the brain – mainly related to the serotonergic system and neurogenesis 62, 71, 78, 88, 91, 97, 127, 129, 141 , gene expression 76, 94, 96, 112, 113, 120, 121, 123, 137, 141, 143 , and epigenetic modifications 76, 112, 114, 124 .…”

Section: Discussionmentioning

confidence: 99%

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Ramsteijn

Wijer

Rando

et al. 2019

Preprint

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AbstractIn the Western world, 2-5% of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) −0.28 [-0.38, −0.18]), more passive stress coping (SMD −0.37 [-0.52, −0.23]), and less efficient sensory processing (SMD −0.37 [-0.69, −0.06]) in SSRI-versus vehicle-exposed animals. No differences were found for anxiety (p=0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects.HighlightsPerinatal SSRI exposure in rodents alters outcomes in three behavioral domains.It leads to reduced activity, passive stress coping, and weaker sensory processing.Females are understudied but seem to be less vulnerable than males.Early postnatal exposure in rodents leads to the largest effects on behavior.This is equivalent to the third trimester of pregnancy in humans.

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Section: Discussionmentioning

confidence: 99%

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Ramsteijn

Wijer

Rando

et al. 2019

Preprint

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“…Body weights were measured at 7th, 14th and 21st day of life, as well as immediately before euthanasia at 60 days of age. Body weights were recorded using an analytical scale (S‐400 with a capacity of 400 g and a readability of 0.01 g; Braz, Freitas, et al., ; Braz, Pedroza, et al., ; Pinheiro et al., ; da Silva et al., ; da Silva, Braz, Silva‐Filho, et al., ; da Silva, Braz, Pedroza, et al., ).…”

Section: Methodsmentioning

confidence: 99%

“…Benmansour, Owens, Cecchi, Morilak, and Frazer (2002) demonstrated that SERT expression is downregulated in the presence of SSRIs (Benmansour et al, 2002), Maciag et al (2006), otherwise, found that chronic treatment with citalopram (i.e., another SSRI) in adult rats did not modulate SERT expression (Maciag et al, 2006). Recent research has indicated that neonatal exposure to fluoxetine, another SSRI, increases SERT gene expression and protein content in the hypothalamus of animals at 21 and 40 days of life (Pinheiro et al, 2017). Studies from our laboratory have highlighted that fluoxetine treatment during critical development period improves mitochondrial function and reduces oxidative stress in several tissues Simoes-Alves et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Serotonin transporter inhibition during neonatal period induces sex‐dependent effects on mitochondrial bioenergetics in the rat brainstem

Silva

Freitas

et al. 2018

Eur J of Neuroscience

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The serotonin reuptake is mainly regulated by the serotonin transporters (SERTs), which are abundantly found in the raphe nuclei, located in the brainstem. Previous studies have shown that dysfunction in the SERT has been associated with several disorders, including depression and cardiovascular diseases. In this manuscript, we aimed to investigate how gender and the treatment with a serotonin selective reuptake inhibitor (SSRI) could affect mitochondrial bioenergetics and oxidative stress in the brainstem of male and female rats. Fluoxetine, our chosen SSRI, was used during the neonatal period (i.e., from postnatal Day 1 to postnatal Day 21-PND1 to PND21) in both male and female animals. Thereafter, experiments were conducted in adult rats (60 days old). Our results demonstrate that, during lactation, fluoxetine treatment modulates the mitochondrial bioenergetics in a sex-dependent manner, such as improving male mitochondrial function and female antioxidant capacity.

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“…e SSRI fluoxetine binds SERT with high affinity and acts primarily by blocking SERT at the presynaptic neuron, thus regulating extracellular 5-HT levels and improving emotional status [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence-Based Complementary and Alternative Medicine to improvements in behavioral parameters of depression in rats [56,57]. Fluoxetine is an SSRI which acts by blocking the 5-HT transporter (SERT) at the presynaptic neuron to regulate extracellular 5-HT levels and improve emotional status [29]. Fluoxetine has been shown to act on 5-HT neurons in the raphe, in turn leading to the reduced expression of miRNA-16 in the hippocampus [58].…”

mentioning

confidence: 99%

Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression

Zhao

Tian

Song

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

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Neonatal fluoxetine exposure modulates serotonergic neurotransmission and disturb inhibitory action of serotonin on food intake

Cited by 15 publications

References 43 publications

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

Serotonin transporter inhibition during neonatal period induces sex‐dependent effects on mitochondrial bioenergetics in the rat brainstem

Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression

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