Rapid and acute effects of estrogen on time perception in male and female rats

Abstract

Sex differences in the rapid and acute effects of estradiol on time perception were investigated in adult male and female Sprague-Dawley rats. Because estradiol has been shown to increase striatal dopamine release, it may be able to modify time perception and timed performance by increasing the speed of an internal clock in a manner similar to indirect dopamine agonists such as amphetamine and cocaine. Two groups of females (neonatally estradiol-treated/adult ovariectomized and neonatally oil-treated/adult ovariectomized) and two groups of males (neonatally castrated and adult castrated) were trained in a 2 vs. 8-s duration bisection procedure and tested using intermediate signal durations. After obtaining oil-injected baseline psychometric functions over several days, rats were administered 5 μg of estradiol for 4 days and behaviorally evaluated 30 min following each injection. This oil-estradiol administration cycle was subsequently repeated three times following the re-establishment of baseline training. Results revealed significant sex differences in the initial baseline functions that were not modifiable by organizational hormones, with males' duration bisection functions shifted horizontally to the left of females'. Upon the first administration of estradiol, females, but not males, showed a significant, transient leftward shift in their bisection functions, indicative of an increase in clock speed. After extensive retraining in the duration bisection procedure, rats that were exposed to gonadal hormones during the first week of life showed a significant rightward shift in their bisection functions on the fourth day of estradiol administration during each cycle, suggesting a decrease in clock speed. Taken together, our results support the view that there are multiple mechanisms of estrogens' action in the striatum that modulate dopaminergic activity and are differentially organized by gonadal steroids during early brain development.

Keywords: clock speed; dopamine; duration bisection; interval timing; sex differences; striatum.

Figure 1

Phase 1 duration baseline bisection function raw data and sigmoidal fits as a function of (A) treatment group (AOF, NEF, ACM, NCM); (B) genetic sex (female = AOF + NEF, male = ACM + NCM); and (C) hormonal sex (female = AOF + NCM, male = ACM + NEF), revealing a non-significant effect of treatment group (p > 0.05), a significant effect of genetic sex (p < 0.05), and a non-significant effect of hormonal sex (p > 0.05). Probability of a “long” response is plotted as a function of signal duration(s).

Figure 2

Phase 1 duration bisection functions during baseline, E1, and E4 for (A) genetic females and (B) genetic males, revealing a significant transient leftward shift in females on E1 that returns to baseline by E4 (p < 0.05), and no effect in males. Probability of a “long” response is plotted as a function of signal duration(s).

Figure 3

Phase 1 sigmoidal function measures of (A) point of subjective equality (PSE) and (B) Weber fractions (WF) for genetic males and females showing a significant effect of estrogen on E1 for females in PSE (p < 0.05) and no effects in WF (p > 0.05).

Figure 4

Phase 2 baseline duration bisection functions. No significant effects were observed in the raw data or sigmoidal fits between (A) treatment groups (p > 0.05); (B) genetic sex (p > 0.05); or (C) hormonal sex (p > 0.05). Probability of a “long” response is plotted as a function of signal duration(s).

Figure 5

Phase 2 duration bisection functions for (A) hormonal females and (B) hormonal males during baseline, E1, E4, and washout (WO), revealing no significant effects in females (p > 0.05), but a significant effect in males on E4 that returned to baseline the following day (WO; p < 0.01). Probability of a “long” response is plotted as a function of signal duration(s).

Figure 6

Phase 2 sigmoidal function measures of (A) point of subjective equality (PSE) and (B) Weber fractions (WF) for hormonal males and females showing a significant effect of estrogen on E4 for males in PSE (p < 0.01) and a main effect of test day for WF (p < 0.001).