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Disorders of the dopamine system, such as schizophrenia or stimulant addiction, are associated with impairments in different forms of cost/benefit decision making. The neural circuitry (ie amygdala, prefrontal cortex, nucleus accumbens) underlying these functions receives dopamine input, which is thought to have a central role in mediating cost/benefit decisions. Estradiol modulates dopamine activity, and estrogen receptors (ERs) are found within this neurocircuitry, suggesting that decision making may be influenced by estradiol. The present study examined the contribution of estradiol and selective ERα and β agonists on cost/benefit decision making in adult female Long-Evans rats. An effort-discounting task was utilized, where rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward lever to obtain four pellets. Ovariectomy increased the choice on the high-reward lever, whereas replacement with high (10 μg), but not low (0.3 μg), levels of estradiol benzoate reduced the choice on the high-reward lever. Interestingly, both an ERα agonist (propyl-pyrazole triol (PPT)) and an ERβ agonist (diarylpropionitrile (DPN)) increased choice on the high-reward lever when administered independently, but when these two agonists were combined, a decrease in choice for the high-reward lever was observed. The effects of estradiol, PPT, and DPN were more pronounced 24 h post-administration, suggesting that these effects may be genomic in nature. Together, these results demonstrate that estradiol modulates cost/benefit decision making in females, whereby concomitant activation of ERα and β receptors shifts the decision criteria and reduces preference for larger, yet more costly rewards. [ABSTRACT FROM AUTHOR]

Estrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. In particular, 17β-estradiol can improve, impair, or have no effect on hippocampus-dependent learning and memory depending on dose and time of administration. The effects of other forms of estrogen, such as estrone and 17α-estradiol, on hippocampus-dependent learning have not been as thoroughly investigated. Therefore, the purpose of this study was to investigate the effects of 17β-estradiol, estrone, and 17α-estradiol at three different doses on two different tasks: hippocampus-dependent contextual fear conditioning and hippocampus-independent cued fear conditioning. Adult ovariectomized female rats were injected with one of the estrogens at one of the three doses 30 mins before conditioning to assess the rapid effects of these estrogens on acquisition. Twenty-four hours later memory for the context was examined and 1 h later memory for the cue (tone) was assessed. Levels of synaptophysin were examined in the dorsal hippocampus of rats to identify a potential synaptic correlate of hormonal effects on contextual fear conditioning. Low 17β-estradiol and 17α-estradiol enhanced, whereas high 17β-estradiol and 17α-estradiol impaired, contextual fear conditioning. Only the middle dose of estrone severely impaired contextual fear conditioning. Estrogens did not alter performance in the hippocampus-independent cued task. Synaptophysin expression was increased by estrone (at a middle and high dose) and 17β-estradiol (at a middle dose) in the CA3 region of the hippocampus and was not correlated with cognition. The results of this study indicate that estradiol can positively or negatively influence hippocampus-dependent learning and memory, whereas estrone impairs hippocampus-dependent learning and memory in a dose-dependent manner. These results have important therapeutic implications, as estrone, a main component of a widely used hormone replacement therapy, was shown to have either a negative effect or no effect on learning and memory. It may be possible to use 17α-estradiol and lower doses of estrogens as potential alternatives in hormone replacement therapies. [ABSTRACT FROM AUTHOR]