Modulatory effect of 17-β estradiol on performance of ovariectomized rats on the Shock-Probe test.

17-β estradiol (E2) has been shown to modulate fear conditioning by influencing freezing behavior following re-exposure to either the conditioning context or a cue associated with shock. Fear-related behaviors other than freezing may be influenced differently by E2 replacement. Accordingly, the present study examined whether E2 modulates fear conditioning using the Shock-Probe test, which allows for the observation of multiple fear responses. Ovariectomized (OVX) rats were divided into three groups: no E2 replacement (Shock-Oil; 0.1ml/kg sesame oil), high E2 replacement (Shock-E2; 3 daily doses of 10μg/kg, s.c.), and a no shock, no E2 replacement (Naïve-oil) group. During the acquisition phase, the two shock groups (Shock-Oil and Shock-E2) demonstrated comparable fear expression on all measures. During the retention tests, rats without E2 replacement demonstrated intact contextual-fear conditioning but impaired cued-fear conditioning, while rats with E2 replacement demonstrated the opposite pattern. In the context paired with shock, the Shock-Oil group spent more time burying the probe than both the Naïve-oil group and Shock-E2 group. The Shock-E2 group avoided the probe area relative to the other two groups when tested in the context unpaired with shock. The present findings demonstrate the importance of using multiple behaviors to measure fear conditioning and suggest that high E2 replacement impairs contextual and facilitates cued fear conditioning.