Intra-striatal estradiol in female rats impairs response learning within two hours of treatment

Estradiol treatment administered systemically or directly to the dorsolateral striatum across two days impairs performance on a response task in which rats learn to make a specific body turn to locate food on a maze. Estradiol can act through both slow and rapid signaling pathways to regulate learning impairments, however it is impossible to dissociate the slow from the rapid contributions of estradiol following long exposures. To assess the rapid effects of estradiol on striatum-sensitive learning, we trained rats on a response learning task after either relatively short or long treatments of estradiol infused directly into the striatum. Three-month-old female rats were ovariectomized 21 days before training and received guide cannulae implanted bilaterally into the dorsolateral striatum. For short duration treatments, rats were given bilateral infusions (0.5 μl) of 17β-estradiol-sulfate (0, 5, 50, or 500 nM in aCSF-vehicle) either 2h or 15 min prior to training. For long duration treatments, rats received a series of estradiol infusions (500 nM) at 48, 24, and 2h prior to training. Replicating previous findings (Zurkovsky et al., 2007), intra-striatal estradiol treatments given for two days prior to training impaired response learning. Estradiol-induced impairments in performance were also demonstrated 2h, but not 15 min, after single infusions. Thus, estradiol acts within hours of exposure in the striatum, a structure lacking classical estrogen receptors, to impair response learning.