Abstract

Estrogen plays an important role in the modulation of cognitive performance in both women and female rodents. These effects may be attributed to the estrogenic modulation of neuroanatomical structures and neurotransmitter systems in the brain, including dopamine. Here, the influence of estrogen on dopamine-mediated behaviors as well as dopamine release and synaptic plasticity were examined. Study 1 showed that latent inhibition is exhibited by females in proestrus, a time of high estrogen, but not by females in estrus or metestrus, periods of low estrogen. Study 2 examined the effects of chronic estradiol (E2) in ovariectomized rats on cognitive strategy. Rats with high levels ofE2 predominantly use a place strategy while rats with low levels of E2 predominantly use a response strategy. Systemic administration of dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) antagonists caused a switch of strategy use in low E2 rats. To determine where in the brain this effect was occurring, Study 3 utilized intracranial infusions of D1Rand D2R antagonists in the dorsal striatum (DS) or ventral striatum. D1R, but not D2R, antagonists in the DS caused a switch in strategy use by low E2 females. This suggests that strategy use in low E2 rats is altered by D2R antagonism in another brain region. To this end, in Study 4 D1R and D2R antagonists were infused into the medial prefrontal cortex (mPFC). Both D1R and D2R antagonism resulted in a switch of strategy use by low E2 rats. In Study 5, in vivo microdialysis was utilized in anaesthetized rats to demonstrate that local infusion of E2 into the DS rapidly increases dopamine transmission. Dual-probe in vivo microdialysis was also used in Study 6 to investigate the effects ofE2 on dopamine transmission in the mPFC. Additionally, Western immunoblotting was conducted to evaluate the effects of E2 on synaptic protein levels. Study 7 examined the role of E2 on performance in a mPFC-mediated working memory task. Together, these studies suggest that estrogen influences cognitive performance in the female rat and that this effect is mediated, in part, by its action in the DS and mPFC.