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Neuroscience and Behavioral Physiology

, Volume 49, Issue 3, pp 341–346 | Cite as

Prenatal Effects of Fluoxetine on Adaptive Behavior and the Cognitive Domain in Male Rats During the Prepubertal Period of Development

  • I. P. ButkevichEmail author
  • V. A. Mikhailenko
Article
  • 11 Downloads

The effects of injections of the selective serotonin reuptake inhibitor fluoxetine or physiological saline to rats during pregnancy (from day 9 to day 20) on behavioral parameters of the tonic pain system, anxiety levels, depression, and cognitive measures were studied in male offspring during the prepubertal period of development. The results demonstrated decreases in body weight in neonatal and 25-day-old males. Improvements in spatial learning ability were seen, though there were no changes in measures of psychoemotional behavior in males in the prepubertal period of development. Comparison of the effects of prenatal administration of fluoxetine and physiological saline on the functional activity of the nociceptive system showed that the serotonin reuptake inhibitor eliminated the effect of invasive stress due to the injection. Chronic injections of the antidepressant fluoxetine during pregnancy did not increase pain sensitivity in male offspring.

Keywords

fluoxetine pregnancy males adaptive behavior cognitive domain prepubertal period rats 

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References

  1. 1.
    I. P. Butkevich, V. A. Mikhailenko, Yu. A. Lavrova, and N. A. Ulanova, “Repeated pain syndrome in inflammation and in neonatal males alters adaptive behavior in the adolescent period of development,” Ros. Fiziol. Zh., 100, No. 11, 1241–1251 (2014).Google Scholar
  2. 2.
    V. A. Mikhailenko, I. P. Butkevich, and M. K. Astapova, “Long-term effects of stressors during the neonatal period of development on the nociceptive system and psychoemotional behavior,” Ros. Fiziol. Zh., 102, No. 5, 540–559 (2016).Google Scholar
  3. 3.
    R. Avitsur, “Increased symptoms of illness following prenatal stress: Can it be prevented by fluoxetine?” Behav. Brain Res., 317, 62–70 (2017).CrossRefGoogle Scholar
  4. 4.
    K. L. Bairy, S. Madhyastha, K. P. Ashok, et al., “Developmental and behavioral consequences of prenatal fluoxetine,” Pharmacology, 79, 1–11 (2007).CrossRefGoogle Scholar
  5. 5.
    F. Boulle, J. L. Pawluski, J. R. Homberg, et al., “Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring,” Horm. Behav., 80, 47–57 (2016).CrossRefGoogle Scholar
  6. 6.
    I. P. Butkevich, L. I. Khozhai, V. A. Mikhailenko, and V. A. Otellin, “Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat,” Reprod. Biol. Endocrinol., No. 1, 96–105 (2003), www.rbej.com.
  7. 7.
    I. P. Butkevich, V. A. Mikhailenko, E. A. Vershinina, et al., “Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences,” Brain Res., 1419, 76–84 (2011).Google Scholar
  8. 8.
    T. M. Cabrera and G. Battaglia, “Delayed decreases in brain 5-hydroxytryptamine 2A/2C receptor density and function in male rat progeny following prenatal fluoxetine,” J. Pharmacol. Exp. Ther., 269, No. 2, 637–645 (1994).Google Scholar
  9. 9.
    R. C. Casper, B. E. Fleisher, J. C. Lee-Ancajas, et al., “Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy,” J. Pediatr., 142, 402–408 (2003).CrossRefGoogle Scholar
  10. 10.
    L. Descarries and M. Riad, “Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT1A receptors and SERT,” Phil. Trans. R. Soc. B., 367, 2416–2425 (2012).CrossRefGoogle Scholar
  11. 11.
    D. Dubuisson and S. G. Dennis, “The formalin test: a quantitative study of the analgesic effects of morphine, meperidine and brain stimulation in rats and cats,” Pain, 4, No. 1, 161–174 (1977).CrossRefGoogle Scholar
  12. 12.
    J. Francis-Oliveira, B. Ponte, A. P. Barbosa, et al., “Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats,” Behav. Brain Res., 252, 195–203 (2013).CrossRefGoogle Scholar
  13. 13.
    P. Gaspar, O. Cases, and L. Maroteaus, “The developmental role of serotonin: news from mouse molecular genetics,” Nat. Res. Nat. Res. Neuroscience, No. 4, 1002–1012 (2003).Google Scholar
  14. 14.
    V. Hendrick, Z. N. Stowe, L. L. Altshuler, et al., “Placental passage of antidepressant medications,” Am. J. Psychiatry, 160, 993–996 (2003).CrossRefGoogle Scholar
  15. 15.
    I. Hervas and F. Artigas, “Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors,” Eur. J. Pharmacol., 358, 9–18 (1998).CrossRefGoogle Scholar
  16. 16.
    V. Kiryanova and R. H. Dyck, “Increased aggression, improved spatial memory, and reduced anxiety-like behaviour in adult male mice exposed to fluoxetine early in life,” Dev. Neurosci., 36, No. 5, 396–408 (2014).CrossRefGoogle Scholar
  17. 17.
    V. Kiryanova, B. McAllister, and R. H. Dyck, “Long-term outcomes of developmental exposure to fluoxetine: A review of the animal literature,” Dev. Neurosci., 35, 437–449 (2013).CrossRefGoogle Scholar
  18. 18.
    L. Knaepen, I. Rayen, T. D. Chartier, et al., “Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague–Dawley rat offspring,” PloS One, 8, No. 2 (2013), e57608 doi:  https://doi.org/10.1371/journal.pone.0057608.CrossRefGoogle Scholar
  19. 19.
    L. J. Lee, “Neonatal fluoxetine exposure affects the neuronal structure in the somatosensory cortex and somatosensory-related behaviors in adolescent rats,” Neurotox. Res., 15, 212–223 (2009).CrossRefGoogle Scholar
  20. 20.
    S. F. Lisboa, P. I. Oliveira, L. C. Costa, et al., “Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation,” Pharmacology, 80, 49–56 (2007).CrossRefGoogle Scholar
  21. 21.
    B. B. McAllister, V. Kiryanova, and R. H. Dyck, “Behavioural outcomes of perinatal maternal fluoxetine treatment,” Neuroscience, 226, 356–366 (2012).CrossRefGoogle Scholar
  22. 22.
    S. Misri, P. Reebye, K. Kendrick, et al., “Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications,” Am. J. Psychiatry, 163, No. 6, 1026–1032 (2006).CrossRefGoogle Scholar
  23. 23.
    T. F. Oberlander, R. Eckstein Grunau, C. Fitzgerald, et al., “Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response,” Pediatr. Res., 51, No. 4, 443–453 (2002).CrossRefGoogle Scholar
  24. 24.
    T. F. Oberlander, J. A. Gingrich, and M. S. Ansorge, “Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence,” Clin. Pharmacol. Ther., 86, 672–677 (2009).CrossRefGoogle Scholar
  25. 25.
    T. F. Oberlander, M. Papsdorf, U. M. Brain, et al., “Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age,” Arch. Pediatr. Adolesc. Med., 164, No. 5, 444–451 (2010).CrossRefGoogle Scholar
  26. 26.
    T. F. Oberlander, W. Warburton, S. Misri, et al., “Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data,” Arch. Gen. Psychiatry, 63, No. 8, 898–906 (2006).CrossRefGoogle Scholar
  27. 27.
    J. D. Olivier, A. H. Akerud, H. Kaihola, et al., “The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring,” Front. Cell. Neurosci., 7, 73 (2013).Google Scholar
  28. 28.
    J. D. A. Oliver, A. Valles, E. van Heesch, et al., “Fluoxetine administration to pregnant rats has long-term consequences for the offspring,” Psychopharmacology (Berl.), 217, 419–432 (2011).CrossRefGoogle Scholar
  29. 29.
    A. K. Podrebarac, E. G. Duerden, V. Chau, et al., “Antenatal exposure to antidepressants is associated with altered brain development in very preterm-born neonates,” Neuroscience, 342, 251–262 (2017).CrossRefGoogle Scholar
  30. 30.
    R. D. Porsolt, M. LePichon, and M. Jalfre, “Depression: a new animal model sensitive to antidepressant treatments,” Nature, 266, 730–732 (1977).CrossRefGoogle Scholar
  31. 31.
    L. V. Toffoli, G. M. Rodrigues, Jr., J. F. Oliveira, et al., “Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat’s offspring: Modulation by folic acid supplementation,” Behav. Brain Res., 265, 142–147 (2014).CrossRefGoogle Scholar
  32. 32.
    R. Vartazarmian, S. Malik, G. B. Baker, and P. Boksa, “Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring,” Psychopharmacology (Berl.), 178, 328–338 (2005).CrossRefGoogle Scholar
  33. 33.
    J. C. Velasquez, N. Goeden, and A. Bonnin, “Placental serotonin: implications for the developmental effects of SSRIs and maternal depression,” Front. Cell. Neurosci., 7, 47 (2013).Google Scholar
  34. 34.
    S. G. Vitale, A. S. Laganà, M. R. Muscatello, et al., “Psychopharmacotherapy in pregnancy and breastfeeding,” Obstet. Gynecol. Surv., 71, No. 12, 721–733 (2016).CrossRefGoogle Scholar
  35. 35.
    C. V. Vorhees, K. D. Acuff-Smith, M. A. Schilling, et al., “A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats,” Fundam. Appl. Toxicol., 23, No. 2, 194–205 (1994).CrossRefGoogle Scholar
  36. 36.
    L. A. M. Welberg and L. R. Seckl, “Prenatal stress, glucocorticoids and the programming of the brain,” J. Neuroendocrinol., 13, 113–128 (2001).CrossRefGoogle Scholar
  37. 37.
    M. Zimmerman, “Committee for Research and Ethical Issues of the IASP, Ethical standards for investigations of experimental pain in animals,” Pain, 16, 109–110 (1983).CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pavlov Institute of Physiology, Russian Academy of SciencesSt. PetersburgRussia

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