Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Chronic stress is a major risk factor for major depressive disorder.
• Agomelatine is an antidepressant acting as a MT(1)/MT(2) receptor agonist and 5-HT(2C) antagonist.
• Limited data exist on agomelatine's effects in stress-compromised brains, particularly concerning hippocampal neurogenesis.

Purpose of the Study:

• To investigate the effects of agomelatine on hippocampal neurogenesis in the chronic mild stress (CMS) model.
• To characterize agomelatine's actions in the context of stress-induced alterations in the brain.

Main Methods:

• Adult male rats were subjected to a 5-week CMS paradigm.
• Agomelatine treatment was administered during the final 3 weeks of the stress period.
• Behavioral tests (sucrose preference, marble burying) and assessment of hippocampal neurogenesis (cell proliferation, survival, doublecortin expression) were performed.

Main Results:

• CMS increased anxiety-like behavior (marble burying) but did not affect sucrose preference.
• CMS significantly decreased newborn cell survival and doublecortin expression in the hippocampus.
• Agomelatine treatment normalized stress-induced deficits in cell survival and partially reversed the reduction in doublecortin expression.

Conclusions:

• Agomelatine demonstrates beneficial effects on hippocampal neurogenesis in a chronic mild stress model.
• These findings suggest agomelatine may counteract stress-induced neurogenic impairments relevant to depression.