Antidepressant-like activities of live and heat-killed Lactobacillus paracasei PS23 in chronic corticosterone-treated mice and possible mechanisms

Brain Res. 2019 May 15;1711:202-213. doi: 10.1016/j.brainres.2019.01.025. Epub 2019 Jan 23.


Emerging evidence indicates that ingestion of specific probiotics, known as "psychobiotics", confer beneficial effects on mental health. This study investigated antidepressant-like effects and possible underlying mechanisms of Lactobacillus paracasei PS23 (PS23), live or heat-killed, in a mouse model of corticosterone-induced depression using fluoxetine as standard drug. PS23 were orally gavaged to mice from day 1 to 41 or fluoxetine from day 17 to 41 and injected with corticosterone from day 17 to 37. After the last corticosterone treatment, anxiety- and depression-like behaviors were tested within 4 days. On day 42, serum and brain tissue were collected 24 min after forced swim stress. Abnormal behavioral changes induced by corticosterone were ameliorated by treatment with live PS23 in open field and sucrose preference tests, with heat-killed PS23 in open field, forced swim and sucrose preference tests, and with fluoxetine in open field and forced swim tests. Furthermore, both live and heat-killed PS23 and fluoxetine reversed corticosterone-reduced protein levels of brain-derived neurotropic factor, mineralocorticoid, and glucocorticoid receptors in the hippocampus. In addition, live PS23 also reverses corticosterone-reduced serotonin levels in hippocampus, prefrontal cortex and striatum; whereas heat-killed PS23 reverses corticosterone-reduced dopamine levels in hippocampus and prefrontal cortex. And fluoxetine normalized reduced corticosterone level in serum. These studies showed that both live and heat-killed PS23 can reverse chronic corticosterone-induced anxiety- and depression-like behaviors and that may provide insights into the mechanism and a potential psychobiotic for depression management.

Keywords: Corticosterone; Depression; Fluoxetine; Gut–brain axis; Mice; Psychobiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Anxiety / drug therapy
  • Anxiety Disorders / drug therapy
  • Behavior, Animal / drug effects
  • Brain / metabolism
  • Corticosterone / analysis
  • Corticosterone / blood
  • Depression / drug therapy*
  • Depressive Disorder / drug therapy
  • Disease Models, Animal
  • Fluoxetine / pharmacology
  • Hippocampus / metabolism
  • Lacticaseibacillus paracasei / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / metabolism
  • Probiotics / pharmacology*
  • Receptors, Glucocorticoid / metabolism
  • Stress, Psychological / metabolism


  • Antidepressive Agents
  • Receptors, Glucocorticoid
  • Fluoxetine
  • Corticosterone