Activation of amygdalar metabotropic glutamate receptors modulates anxiety, and risk assessment behaviors in ovariectomized estradiol-treated female rats

Abstract

Anxiety disorders are more prevalent in females than males. The underlying reasons for this gender difference are unknown. Metabotropic glutamate receptors (mGluRs) have been linked to anxiety and it has been shown that interaction between estrogen receptors and mGluRs modulate sexual receptivity in rats. We investigated the role of mGluRs in anxiety-related behaviors in ovariectomized female rats with (OVX+EB) or without (OVX) estradiol implants. We centrally infused (s)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR agonist, into the basolateral amygdala (BLA) of OVX+EB and OVX rats at 0.1 and 1.0μM. Male rats that normally have low estradiol levels were used to compare with OVX rats. Generalized anxiety, explorative activity and detection and analysis of threat were analyzed in the elevated plus maze (EPM) and risk assessment behaviors (RABs). DHPG (1.0μM) increased the percentage of time spent in- and entries into- the open arms in OVX+EB, but not in OVX or male rats. Flat-back approaches and stretch-attend postures, two RABs, were significantly reduced by DHPG (0.1 and 1.0μM) in OVX+EB rats only. DHPG did not modulate rearing and freezing, behaviors related to exploration and fear-like behavior, respectively. However, DHPG (1.0μM) increased head dipping and decreased grooming behaviors in OVX rats, suggesting a weak explorative modulation. The effects of DHPG observed in OVX+EB, were blocked by 50μM of (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), a mGluR1 antagonist. AIDA and/or estradiol did not modulate anxiety and or RABs. Our results show that intra-BLA infusion of DHPG exerts an anxiolytic-like effect in OVX+EB, but not in OVX or male rats. This effect seems to depend upon mGluR1 subtype activation. Our findings led us to suggest that the effects observed in OVX+EB rats might be due to an interaction at the membrane level of estrogen receptors with mGlu1 within the BLA.