Sex differences on the response to antidepressants and psychobiotics following early life stress in rats

Pharmacol Biochem Behav. 2022 Oct:220:173468. doi: 10.1016/j.pbb.2022.173468. Epub 2022 Sep 27.

Abstract

Major depressive disorder (MDD) is the most prevalent mood disorder globally. Most antidepressants available for the treatment of MDD increase the concentration of monoamines in the synaptic cleft. However, such drugs have a high latency time to obtain benefits. Thus, new antidepressants with fast action and robust efficacy are very important. This study evaluated the effects of escitalopram, ketamine, and probiotic Bifidobacterium infantis in rats submitted to the maternal deprivation (MD). MD rats received saline, escitalopram, ketamine, or probiotic for 10, 30, or 50 days, depending on the postnatal day (PND):21, 41, and 61. Following behavior, this study examined the integrity of the blood-brain barrier (BBB) and oxidative stress markers. MD induced depressive-like behavior in females with PND21 and males with PND61. All treatments reversed depressive-like behavior in females and escitalopram and ketamine in males. MD induced an increase in the permeability of the BBB, an imbalance between oxidative stress and antioxidant defenses. Treatments regulated the oxidative damage and the integrity of the BBB induced by MD. The treatment with escitalopram, ketamine, or probiotics may prevent behavioral and neurochemical changes associated with MDD, depending on the developmental period and gender.

Keywords: Blood-brain barrier; Ketamine; Major depressive disorder; Oxidative stress; Probiotic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents* / therapeutic use
  • Antioxidants / metabolism
  • Depressive Disorder, Major* / drug therapy
  • Escitalopram
  • Female
  • Ketamine
  • Male
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Stress, Psychological* / drug therapy

Substances

  • Antidepressive Agents
  • Antioxidants
  • Ketamine
  • Escitalopram