4.1 Article

Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats

Journal

Publisher

WILEY
DOI: 10.1002/jdn.10087

Keywords

anxiety; brain-derived neurotrophic factor; novel object recognition memory; para-chlorophenylalanine; postnatal days; serotonin

Funding

  1. Ardabil University of Medical Sciences, Ardabil, Iran [ARUMS.REC.1398.037]

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The study revealed that serotonin has significant effects on neurodevelopment, cognitive functions, and behavior in rats. Administration of para-chlorophenylalanine (PCPA) during the early postnatal period resulted in impaired short-term novel object recognition memory, increased anxiety-like behaviors, enhanced pain sensitivity, and decreased BDNF levels in the hippocampus and prefrontal cortex.
A survey of the literature indicates that the developmental disruptions in serotonin (5-HT) levels can influence the brain development and the function. To the best of our knowledge, so far, there are a few studies about the effects of developmental period 5-HT depletion on cognition and behavior of adult male and female rats. Therefore, in the present study, we examined the effects of postnatal days (PND 10-20) administration of para-chlorophenylalanine (PCPA, 100 mg/kg, s.c) a 5-HT synthesis inhibitor, on anxiety-related behaviors, pain sensitivity, short-term recognition memory, and hippocampal and prefrontal cortex (PFC) brain-derived neurotrophic factor (BDNF) mRNA expression in adult male and female rats. Novel object recognition memory (NORM) and behavioral parameters (anxiety-like behaviors and pain sensitivity) were evaluated in early adulthood and after that, the hippocampi and PFC of the rat's brain were removed for the determination of BDNF mRNA expression. Our results indicated that the postnatal period administration of PCPA impaired short-term NORM. The postnatal developmental period treatment with PCPA also increased anxiety-like behaviors in the open field and elevated plus maze (EPM) tests. Postnatal PCPA treatment increased pain sensitivity in the hot plate test in both male and female rats, especially in female animals. In addition, postnatal days serotonin depletion decreased BDNF level in the hippocampus and PFC of both male and female rats. These findings demonstrate that serotonin plays the main role in neurodevelopment, cognitive functions, and behavior. Therefore, serotonergic system dysregulation during the developmental periods may have more adverse influences on the brain development of rats.

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