Estradiol and Metabotropic Glutamate Receptors interaction within the anxiety neural circuitry at behavioral and protein levels

Anxiety is the most common psychiatric disorders affecting females twice more than males. In hippocampal cells, estradiol regulates group I/II metabotropic glutamate receptors (mGluR1a/5 and mGluR2/3, respectively) activation. Thus, estradiol might modulate female anxiety within the basolateral amygdala (BLA) through mGluRs. We hypothesized that: 1) BLA activation of mGluRs might produce anxiolytic‐like effects; and 2) mGluR protein expression will be up‐regulated, in an estradiol dependent manner. Ovariectomized female rats, with (OVX+EB) and without (OVX) estradiol treatment were compared to male rats. We infused (S)‐3,5‐dihydroxyphenylglycin (DHPG), a group I mGluR agonist into the BLA. Anxiety was analyzed with the elevated plus maze and risk assessment behaviors (RABs); and protein expression by western blots analysis. DHPG (1.0 μM) increased the time and entries in open arms; and reduced RABs in OVX+EB (p<0.05), but not OVX and/or male rats. In the amygdala, protein expression of mGluR1a and mGluR2/3 were up‐regulated in OVX+EB (p<0.05) than OVX and/or male rats. No differences were found for mGluR5. Thus, activation of group I mGluRs, within the BLA, depends upon estradiol to modulate female anxiety. This effect might be underlined by region‐specific estradiol genomic and nongenomic effects. Grant Funding Source : NIH‐EARDA 1G11H046326, MBRS‐RISE GM61838 and NSF DBI‐0932955