Abstract

The present thesis examined the role of ovarian hormones and reproductive experience on multiple memory system bias in female rats and women. First, the effect of 17β-Estradiol (E2) and parity on learning in a dorsal striatum- (DS) mediated response task and a hippocampus- (HPC) mediated place task was investigated. Ovariectomized (OVX) nulliparous and primiparous female rats receiving low or high E2 replacement were trained on both tasks. Nulliparous rats in the low E2 group learned the response task significantly faster than the place task; this facilitatory effect of low E2 on response learning was not observed in primiparous rats, which suggests that the E2-induced effect on response learning disappears with parity. Dopamine (DA) D1 and D2 type receptor (D1R and D2R, respectively) binding was then investigated in the DS and NAcc core and shell of nulliparous and primiparous OVX rats receiving low or high E2 replacement. Primiparous rats had significantly lower D2R binding in the DS than nulliparous rats. These results hint at a possible DS D2R mechanism in altered response learning in reproductively experienced rats.
Second, the effects of E2 and parity on memory bias in humans was investigated. Young, naturally cycling women with and without reproductive experience were tested on the 4-on-8 virtual maze (4/8 VM) task, which can be solved by using response or spatial memory, during the follicular phase (first half of the menstrual cycle) or the luteal phase (second half). Menstrual cycle results revealed predominant use of spatial memory in the luteal phase group, whereas response memory was associated with the follicular phase, showing that memory bias shifts with cyclic changes in ovarian hormones. Moreover, this pattern was also observed and found to be more pronounced in reproductively experienced women. However, mothers and non-mothers differed in terms of learning the 4/8 VM task, which indicates that there were parity-induced differences despite similar cycle-dependent memory bias. Finally, the role of E2, progesterone (P), and testosterone (T) on this cycle-dependent shift in strategy in mothers and non-mothers was investigated. Results revealed that the follicular phase was associated with low P levels, whereas the luteal phase was linked to a high P state, suggesting that the shift in strategy across the menstrual cycle could be P-mediated in humans. Though not significant, high E2 levels were associated with response memory. Also, the results revealed that P and T both play a significant role in multiple memory system bias; this effect is reversed with parity. Thus, memory bias changes across the menstrual cycle, P and T could have a larger impact than E2 on this shift in humans, and the hormonal profile that underlies this effect is different in reproductively experienced women.