Two days but not 30 min of estradiol replacement restores the response to cocaine in ovariectomized mice. Time course of automatically recorded ambulations (a) and fine movements (b) during habituation and after injections of saline, vehicle/E2, and 30 mg/kg COC in Sham and Ovx mice administered vehicle or E2 starting 2 days or 30 min prior to COC. (c) Percentage of high and low responders in Sham, Ovx, and E2-replaced mice after 30 mg/kg COC based on behavioral observations. (d) Uterine wet weights after behavioral testing. *denotes different from Sham, ~different from Ovx. n = 29–30 per group for Sham, Ovx, and 2 day; n = 15 for 30 min group in (a–c). n = 22–30 per group for Sham, Ovx, and 2 day; n = 8 for 30 min group in (d). X-axis labels: Sal = saline injection, E2 = vehicle or E2 injection, COC = 30 mg/kg COC injection.