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Pre-weaning fluoxetine exposure caused anti-depressant like behavior at adulthood via perturbing tryptophan metabolism in rats

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Abstract

The perinatal depression exposes the child to antidepressants during vulnerable window of development, which can chronically impact the mental wellbeing of new born. Active pharmaceuticals are not tested for this long term neurobehavioral aspect of toxicity during drug development process. Keeping this in view, the current study was designed to study the effect of pre-weaning fluoxetine exposure on depression-like behavior of the offspring upon attaining adulthood using FST (Forced swim test). Additionally, the brain tryptophan, 5-HT (5-hydroxytryptamine) and its metabolite 5-HIAA (5-hydroxyindoleacetic acid) levels were quantified using Enzyme linked Immunosorbent Assay (ELISA), while expression of SERT (serotonin receptor), 5-HT1A receptor, TPH (tryptophan hydroxylase) genes were monitored using qPCR. Our data showed that pre-weaning fluoxetine (10, 50 or 100 mg/kg) exposure decreased depression-like behavior. The 5-HT and 5-HIAA levels showed declining trend. However, the 5-HT synthetic precursor i.e. tryptophan levels were found to be significantly elevated in both brain and plasma as compared to control rats. The gene expression study did not reveal any significant alterations as compared to control. In conclusion, the present study demonstrate that pre-weaning fluoxetine exposure decreased depression-like behavior upon adulthood via perturbing tryptophan metabolism.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to fact that the study is the part of ongoing research but are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan

    Nadeem, Uzair Nisar & Ghulam Abbas

  2. Institute of Pharmacy, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Pakistan

    Nadeem

  3. Department of Research, Ziauddin University, Karachi, Pakistan

    Shumaila Usman & Rehan Imad

  4. Dr. Panjwani Center for Molecular Medicine & Drug Research, ICCBS, University of Karachi, Karachi, Pakistan

    Irfan Khan

Authors
  1. Nadeem
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  2. Shumaila Usman
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  3. Rehan Imad
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  4. Uzair Nisar
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  5. Irfan Khan
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  6. Ghulam Abbas
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Contributions

Following are the author’s contribution in the submitted work: All experiments were performed by Nadeem. The gene expression and ELISA work was assisted by Shumaila Usman, Irfan Khan and Rehan Imad. The data presentation and statistical analysis was helped by Uzair Nisar. Entire word was conceptualized and supervised by Ghulam Abbas. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ghulam Abbas.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University (Approval No. 2019–004).

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The authors have no relevant financial or non-financial interests to disclose.

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Nadeem, Usman, S., Imad, R. et al. Pre-weaning fluoxetine exposure caused anti-depressant like behavior at adulthood via perturbing tryptophan metabolism in rats. Metab Brain Dis 37, 1415–1422 (2022). https://doi.org/10.1007/s11011-022-00951-4

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  • DOI: https://doi.org/10.1007/s11011-022-00951-4

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