Estradiol modulates effort-based decision making in female rats Uban, Kristina A.; Rummel, Julia; Floresco, Stan B.; Galea, Liisa A. M.
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 (i.e. amygdala, prefrontal cortex, nucleus accumbens) underlying these functions all receive dopamine input, which is thought to play 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 choice on the high-reward lever, while replacement with high (10 μg), but not low (0.3 μg), levels of estradiol benzoate reduced choice on the high-reward lever. Interestingly, both an ERα agonist (PPT) and an ERβ agonist (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 hr 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 decision criteria and reduces preference for larger, yet more costly rewards.
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