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Female rats were ovariectomized (OvX) and either oil vehicle (0), or E2 (0.25, 2.5 or 25\u03bcg\/0.1ml vehicle) was injected s.c. two consecutive days of every four days for five cycles before testing. Either 4, 24, 48 or 96h after the last injection, nociception was evaluated on the 50\u00b0C hotplate and warm water tail withdrawal tests before and after escalating doses of s.c. morphine. Lordosis behavior and uterine weight were assessed in other rats at the same E2 doses and time points. E2 significantly lengthened latency to respond on the hotplate test at 24h after the last injection, but had no significant effect on tail withdrawal latencies. The lower doses of E2 significantly increased morphine antinociceptive potency at 4\u201324h on one or both tests, but the intermediate E2 dose significantly<jats:italic>decreased<\/jats:italic>morphine potency at 48h on the hotplate test. Thus, E2 modulation of morphine antinociception in the adult female rat is bidirectional, and occurs at E2 doses producing cyclic changes in sexual behavior, uterine weight and vaginal cytology that are similar to those observed in gonadally intact, cycling females.<\/jats:p>","DOI":"10.1016\/j.ejpain.2007.07.014","type":"journal-article","created":{"date-parts":[[2007,9,17]],"date-time":"2007-09-17T12:21:45Z","timestamp":1190031705000},"page":"472-479","source":"Crossref","is-referenced-by-count":39,"title":["Dose\u2010 and time\u2010dependent estradiol modulation of morphine antinociception in adult female rats"],"prefix":"10.1002","volume":"12","author":[{"given":"Rebecca M.","family":"Craft","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ulibarri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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