The Effects of Estradiol and Progesterone Replacement on the Conditioning of Anticipatory Nausea in Ovariectomized Female Rats

Chemotherapy patients frequently develop anticipatory nausea (AN), a conditioned response in which nausea occurs prior to treatment. AN is more prevalent in females, with estradiol and progesterone being implicated in this sex difference. This study investigated the effects of estradiol and progesterone replacement on AN in ovariectomized female rats using a lithium chloride (LiCl) context-conditioning paradigm. Rats received estradiol, progesterone, combined hormone treatment, or oil vehicle, and conditioned gaping behaviour, a validated index of nausea, was measured. Rats receiving combined estradiol and progesterone treatment exhibited significantly greater gaping behaviour compared to all other groups, especially with a higher dose of LiCl. In contrast, estradiol or progesterone alone did not significantly enhance gaping and in some cases suppressed it. These findings suggest that the combined presence of estradiol and progesterone facilitates the learning and expression of anticipatory nausea, while each hormone alone may be insufficient to drive this effect.