Accumulating evidence suggests a role for estrogen in the use of a particular cognitive strategy when solving a maze task. In order to confirm the role of estrogen in this phenomenon, ovariectomized (OVX) female rats receiving either high ( approximately 90 pg/ml) or low ( approximately 32 pg/ml) circulating levels of 17beta-estradiol benzoate (E2) performed a plus maze task for a reward. Consistent with previous research, OVX rats receiving low levels of E2 utilized a striatum-mediated response strategy while OVX rats administered high levels of E2 employed a hippocampus-mediated place strategy. Furthermore, following a systemic injection of a moderate dose of either a dopamine D1 (SKF 83566, 0.1 mg/kg IP) or D2 (raclopride, 0.5 mg/kg IP) receptor antagonist, low E2 rats were seen to use the opposite strategy and exercise a hippocampus-mediated place strategy in order to obtain the reward. At the same doses, high E2 rats did not change from using a place strategy. At a lower dose, these drugs shifted high E2 rats such that they showed an equal propensity for either strategy; this was not observed in low E2 rats. These results corroborate previous findings that E2 plays a significant role in the use of either a response or place strategy when solving a maze for a reward. In addition, the shift in strategy after dopamine receptor blockade implies the importance of central dopamine function in selecting a cognitive strategy to solve such tasks. It is suggested that estrogen alters cognitive strategy not only by improving hippocampal function, but also by altering dopamine-regulated striatal function.

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Studies in both rodents and humans have made much progress in shedding light on how fluctuations in ovarian hormones can affect memory in women across the lifespan. Specifically, advances in neuroscience have identified multiple memory systems that are each mediated by different brain areas. Two memory systems used to navigate an environment are 'place' and 'response' memory. They are defined as either using an allocentric strategy: using a spatial or cognitive map of the surroundings, or an egocentric strategy: using habitual-turns/ movements, respectively. Studies in neuroendocrinology have shown that estrogen levels can bias a female to use one memory system over another to solve a task, such that high estrogen levels are associated with using place memory and low levels with using response memory. Furthermore, recent advances in identifying and localizing estrogen receptors in the rodent brain are uncovering which brain regions are affected by estrogen and providing insight into how hormonal fluctuations during the menstrual cycle, pregnancy, and menopause might affect which memory system is facilitated or impaired in women at different life stages. These studies can help point the way to improving cognitive health in women. Estrogen and cognitionModern Western society is not only marked by longer life expectancies, but young women are also waiting longer to have children and having fewer of them, therefore having more menstrual cycles in their lifetimes than ever before. Progesterone (P) and 17β-estradiol (E2; the most potent of the estrogens during reproductive years) vary across the menstrual cycle in a consistent and fluctuating manner.During the first half of the cycle, or follicular phase, E2 and P levels are low; E2 levels then start to increase steadily at the end of menstruation, reaching a peak in the middle of the menstrual cycle, right before ovulation occurs. This is followed by the luteal phase, when E2 levels plateau while P levels increase and peak until menstruation begins again (Figure 1). Thus, E2 and P work hand in hand across a woman's cycle to orchestrate menstruation, ovulation, and conception.However, these hormones appear to be exerting other effects on the female brain, which could be subject to subtle changes as hormone levels fluctuate over time. human menstrual cycle (top panel) and the ~4 day rat estrous cycle (bottom panel). Human menstrual cycle begins with a follicular (mentrual and preovulatory) phase, followed by ovulation, and ends with a luteal phase (spanning end of ovulation to pre-menstrual phase).

Dopamine (DA) transmission in the medial preoptic area (mPOA) plays a critical role in the control of appetitive sexual behaviour in the female rat. We have shown previously that a DA D1 receptor (D1R)-mediated excitatory state appears to occur in females primed with estradiol benzoate (EB) and progesterone (P), whereas a DA D2 receptor (D2R)-mediated inhibitory state appears to occur in females primed only with EB. The present experiment employed three techniques to better understand what changes occur to DA receptors (DARs) in the mPOA under different hormonal profiles. Ovariectomized females were randomly assigned to one of three steroid treatment groups: EB + P (10 and 500 μg, respectively), EB + Oil, or the control (Oil + Oil), with hormone injections administered at 48 and 4 h prior to euthanizing. First, the number of neurons in the mPOA that contained D1R or D2R was assessed using immunohistochemistry. Second, the mPOA and two control areas (the prelimbic cortex and caudate putamen) were analysed for DAR protein levels using western blot, and DAR functional binding levels using autoradiography. Ovarian steroid hormones affected the two DAR subtypes in opposite ways in the mPOA. All three techniques supported previous behavioural findings that females primed with EB have a lower D1R : D2R ratio, and thus a D2R-mediated system, and females primed with EB + P have a higher D1R : D2R ratio, and thus a D1R-mediated system. This provides strong evidence for a DA-driven pathway of female sexual motivation, desire, and behaviour that is modified by different hormone priming regimens.

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