Acute 17β-Estradiol Administration Enhances Fear Extinction Memory and Alters Gut Microbiota in Female Rats.

Area of Science:

• Neuroscience
• Microbiology
• Endocrinology

Background:

• Ovarian hormones, including 17β-estradiol (E2), influence fear extinction memory and the gut microbiome.
• Elevated E2 levels during fear extinction learning enhance recall 24 hours later.
• This study investigates the long-term maintenance of E2's facilitative effect on fear extinction and the gut microbiome's mediating role.

Purpose of the Study:

• To examine the long-term impact of 17β-estradiol (E2) on fear extinction memory consolidation.
• To investigate the role of the gut microbiome as a potential mediator of E2's effects on fear extinction.
• To explore potential therapeutic targets for anxiety and fear-based disorders.

Main Methods:

• Naturally cycling female Sprague Dawley rats were used in an auditory-cued fear conditioning/extinction paradigm.
• Estrus cycle was tracked, and fecal samples were collected.
• Rats received either E2 (15 μg/kg) or a vehicle 24 hours before extinction training, with recall assessed at 24 hours and 1-2 weeks post-training.

Main Results:

• E2-treated rats exhibited significantly reduced freezing behavior during recent recall (24 hours post-training) compared to controls.
• This facilitation was not observed during remote recall (1-2 weeks post-training).
• 16S rRNA sequencing revealed distinct gut bacterial families, including estrogen-regulating and anxiety-related ones, were enriched during remote recall in E2-treated rats.

Conclusions:

• E2-enhanced fear extinction consolidation may be associated with gut microbiome alterations.
• These findings suggest the gut microbiome as a potential mediator of hormonal effects on fear memory.
• The gut microbiome presents a novel therapeutic target for anxiety and fear-related psychiatric conditions.