Administration of estrogen receptor beta-specific selective estrogen receptor modulators to the hippocampus decrease...

Area of Science:

• Neuroscience
• Endocrinology
• Psychiatry

Background:

• Sex differences in neuropsychiatric disorders often emerge post-puberty.
• Estrogen receptor beta (ERbeta) plays a role in estradiol's (E(2)) effects on anxiety and depressive behaviors.

Purpose of the Study:

• To investigate if ERbeta in the hippocampus mediates the anti-anxiety and anti-depressive effects of E(2).
• To determine if selective estrogen receptor modulators (SERMs) targeting ERbeta in the hippocampus can reduce anxiety and depressive behaviors.

Main Methods:

• Ovariectomized rats were surgically implanted with cannulae targeting the hippocampus or ventral tegmental area.
• Rats received vehicle, E(2), ERalpha-selective SERMs, or ERbeta-selective SERMs in the target or control regions.
• Behavioral tests included the open field, elevated plus maze (anxiety), and forced swim test (depression).

Main Results:

• ERbeta-selective SERMs administered to the hippocampus, but not the ventral tegmental area, decreased anxiety and depressive behaviors.
• E(2) and ERbeta-selective SERMs increased exploration in the open field and elevated plus maze and decreased immobility in the forced swim test.
• ERalpha-specific SERMs did not produce significant anxiolytic or antidepressant effects compared to vehicle.

Conclusions:

• Estrogen's anti-anxiety and anti-depressive effects appear to be mediated by ERbeta within the hippocampus.
• Targeting hippocampal ERbeta may represent a therapeutic strategy for neuropsychiatric disorders with sex-specific prevalence.