Effect of the acute and chronic estrogen on anxiety in the elevated T-maze

Despite the extensive studies on the influences of estrogen (E2) on anxiety-like behaviors, there is still conflicting evidence regarding the specific effects of E2 on anxiety. These discrepancies may be a result of different replacement regimens. The goals of this study were to evaluate anxiety-like behavior in ovariectomized rats (Ovx) using the elevated T-maze (ETM) test for the following variables: (1) the effects of acute versus chronic E2 dosing, (2) the effects of chronic E2 at different doses and, (3) the effects of Tamoxifen (Tam) co-administered with E2. Rats in the acute E2 dosing group (aE2) showed reduced inhibitory avoidance responses with prolong escape latencies compared to Ovx; while rats in the chronic E2 dosing group (cE2) showed reduced inhibitory avoidance responses only. These results suggest that E2 contains anxiolytic effects when given once or repeatedly. Moreover, when various doses of E2 (1-100 μg/kg) were chronically given to the Ovx rats, all doses produced impaired inhibitory avoidance responses compared to Ovx, suggesting that chronic replacement of E2 had no dose-dependent effect on anxiety-like behavior. Interestingly, in the 3-week delay replacement regimen, the low dose E2 (1 μg/kg, s.c.) group displayed no anxiolytic effects as their inhibitory avoidance responses in the ETM were not different from their Ovx counterparts. On the contrary, the Ovx group that received Tam + E2 (Tam 1 mg/kg, PO and E2 1 μg/kg, s.c.) had reduced inhibitory avoidance responses compared to other groups. These findings indicate that when Tam is co-administered with chronic low dose estrogen, it can act as an estrogen receptor agonist and result in anti-anxiety effects. Therefore, it is likely that the anxiolytic-like behavior relative to generalized anxiety disorder can be conserved when estrogen is given acutely or chronically; while the anxiolytic-like behavior relative to panic disorder can be conserved only when estrogen is given acutely.

► In the Ovx rats, both acute and chronic E2 conserved anxiolytic effect. ► The anxiolytic effect was not depended on the E2 doses when given chronically. ► Tamoxifen acted in concert with E2 as an ER agonist resulting in anxiolytic effect.