Intrauterine and lactation exposure to fluoxetine blunted in the offspring the aortic adaptive response induced by acute restraint stress

Eur J Pharmacol. 2017 Oct 15:813:147-152. doi: 10.1016/j.ejphar.2017.08.018. Epub 2017 Aug 17.

Abstract

Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation. The experiments were performed in adult male offspring, treated or not with reserpine (4mg/Kg, ip, 28h before the experimental protocol). Fluoxetine and control rats were submitted to a single restraint stress session (ST) for 1h. Curves to phenylephrine were performed in thoracic aorta with endothelium. Aortic nitric oxide (NOx) were evaluated by the Griess method. The aortic contraction induced by phenylephrine was similar between control and fluoxetine rats. The acute stress reduced contraction in aorta of control ST compared to control, and L-NAME equaled this response. In fluoxetine rats, ST did not change the aortic constriction. Reserpine treatment restored the vasoconstriction in control ST, but did not interfere with aortic contraction in control, fluoxetine or fluoxetine ST. The NOx concentration was higher in aortas from control ST than control rats, and reserpine reduced NOx levels of control ST. The NOx concentration was similar between fluoxetine and fluoxetine ST rats, treated or not with reserpine. In conclusion, maternal treatment with fluoxetine blunted acute restraint stress-induced NO system activation and aortic adaptation in adult offspring.

Keywords: Acute restraint stress; Antidepressant; Maternal treatment; Nitric oxide; Vascular reactivity.

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Aorta / drug effects
  • Aorta / physiopathology*
  • Female
  • Fluoxetine / pharmacology*
  • Lactation*
  • Male
  • Nitric Oxide / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Wistar
  • Restraint, Physical / psychology
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism
  • Uterus / drug effects*
  • Uterus / physiopathology*
  • Vasoconstriction / drug effects

Substances

  • Fluoxetine
  • Nitric Oxide