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

Despite the extensive studies on the influences of estrogen (E(2)) on anxiety-like behaviors, there is still conflicting evidence regarding the specific effects of E(2) 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 E(2) dosing, (2) the effects of chronic E(2) at different doses and, (3) the effects of Tamoxifen (Tam) co-administered with E(2). Rats in the acute E(2) dosing group (aE(2)) showed reduced inhibitory avoidance responses with prolong escape latencies compared to Ovx; while rats in the chronic E(2) dosing group (cE(2)) showed reduced inhibitory avoidance responses only. These results suggest that E(2) contains anxiolytic effects when given once or repeatedly. Moreover, when various doses of E(2) (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 E(2) had no dose-dependent effect on anxiety-like behavior. Interestingly, in the 3-week delay replacement regimen, the low dose E(2) (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+E(2) (Tam 1 mg/kg, PO and E(2) 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.