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10h ago

Developmental Timing and Sex Determine Long-Term Effects of Fluoxetine in Rats

Adult nicotinamide supplementation reversed depression-like behaviors caused by early postnatal fluoxetine treatment.

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The researchers point out that the impact on neuronal bioenergetics is likely critical, as the long-lasting increase in depressive behavioral responses noted with early postnatal fluoxetine treatment could be reversed by adult-onset nicotinamide (vitamin B3), a NAD+ precursor that enhances mitochondrial bioenergetics treatment. Credit: Neuroscience News

Overview

  • Early postnatal fluoxetine exposure (P2–P21) in male rats led to persistent increases in anxiety- and depression-like behaviors in adulthood.
  • Adolescent fluoxetine treatment (P28–P48) in male rats produced opposite outcomes, reducing anxiety- and depression-like behaviors six months later.
  • Divergent mood effects corresponded with distinct changes in gene expression, neuronal architecture, and bioenergetic levels in the medial prefrontal cortex.
  • Adult-onset nicotinamide (vitamin B3) supplementation restored prefrontal bioenergetics and reversed depressive behaviors induced by early-life fluoxetine.
  • Researchers are calling for translational studies to identify sensitive developmental windows in humans and inform pediatric SSRI prescribing strategies.