Estrogen-induced changes in place and response learning in young adult female rats.

Abstract

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-microg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems.

Chronic stress enhances spatial memory in ovariectomized female rats despite CA3 dendritic retraction: Possible involvement of CA1 neurons

“…Within 48 h of administering 17β-estradiol, CA1 spine density increases and these maximal levels are maintained for an additional 48 h after estrogen is metabolized, then density slowly declines over the next few days (Woolley and McEwen, 1993;Woolley, 1998). While the 17β-estradiol dose used in this study (0.1 mL of 5 μg) is similar to that which has been used in other behavioral paradigms (Chesler and Juraska, 2000;Korol and Kolo, 2002), this dose is too low to fully reproduce increases in CA1 apical spine density which have been demonstrated in morphological studies (0.1 mL of 10 μg; Gould et al, 1990;Woolley and McEwen, 1993;Woolley, 1998). Therefore, estrogen treatments used in future research will need to include higher doses in order to determine a more clear relationship between changes in the brain and subsequent behavior.…”

“…Acute estrogen replacement can be given 3 weeks to 4 months after OVX to observe changes in memory (Korol and Kolo, 2002;Sandstrom and Williams, 2004). Administering 17β-estradiol to OVX females either 72 and 48 h, or 48 and 24 h before behavioral assessment, which is consistent with our time frame, can either improve or impair spatial memory, depending on the task, compared with controls (Frye, 1995;Sandstrom and Williams, 2001;Korol and Kolo, 2002). Perhaps our handling procedure may have negated estrogen's effects on the Y-maze because of the enriched setting.…”

“…Injections were given to each rat at 48 h and then again at 24 h prior to behavioral training on the Y-maze, a schedule designed to parallel estrogen levels similar to those in proestrus (Chesler and Juraska, 2000;Korol and Kolo, 2002). The 4 week delay between OVX and estrogen treatment is within the 2-8 week window that acute estrogen replacement has been previously shown to effectively influence behavior (Becker et al, 1987;Frye, 1995;Korol and Kolo, 2002;Markham et al, 2002). Injections coincided with the last two days of restraint, and were administered to the animals between 8 and 9 AM before restraint started.…”

Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene

“…Estradiol regulates PFC blood flow in humans (Berman et al 1997), and Korol (2002;2004) has demonstrated that E2 biases toward or against the activation of circuits mediating different forms of cognition: high estrogen favoring place-activated learning and low estrogen levels response-dependent learning. It is tempting to speculate, therefore, that disturbed ER alpha signaling in the luteal phase may interact with decreased PFC efficiency in those with the Val/ Val genotype so as to permit the expression of a dysphoric state suggestive of disinhibited subcortical (e.g., amygdala) activity.…”

Hippocampal volume and functional connectivity changes during the female menstrual cycle

“…Because the hippocampus has been demonstrated to be one of the main hormone-sensitive targets in the brain, hippocampus dependent cognitive functions, such as spatial-memory tasks, were investigated. Results are mixed, showing differences in associations to endogenous and exogenous hormonal variation, dose-and durationspecific reactions, and interactions between different gonadal hormones on cognitive functions (e.g., Bimonte and Denenberg, 1999;Chesler and Juraska, 2000;Gibbs, 2000;Korol and Kolo, 2002;O'Neal et al, 1996;Stackman et al, 1997). Some studies find evidence for decreased spatial abilities (i.e., spatial learning and spatial recognition memory) in high-estrogen phases during the cycle (e.g., Galea and Kavaliers, 1995;Lacreuse et al, 2001).…”