Research

The role of estrogen receptors in maladaptive reward processing

The Georgiou lab aims to study the role of estradiol (E2) in the hypogonadism-induced risk of developing mood disorders. It was previously shown that E2 through its action on brain estrogen receptors (ERs) plays a central role in maladaptive behaviors and it was also demonstrated that activation of the ERβ-expressing neurons can induce a reward response in a sex-dependent manner. The lab intends to explore the effectiveness of targeting the ERs (ERα, ERβ, and GPER) in specific brain circuits in both sexes for inducing antidepressant effects and reversing maladaptive reward processing. We will use interdisciplinary techniques, including in vitro slice electrophysiology, optogenetics, chemogenetics, and in vivo fiber photometry, to characterize the synaptic properties of the ERβ-expressing BLA inputs to NAc. We will also study the potential involvement of other BLA microcircuits and the interaction of ERα and GPER with ERβ.

The Georgiou lab will also explore the role of ERβ in opioid addiction and associated disorders. We will use molecular, imaging, electrophysiological, and behavioral techniques to study the involvement of ERα, ERβ, and GPER in chronic opioid administration, withdrawal, and relapse in both male and female mice. The lab will also examine the impact of ERβ dysregulation on the oxytocin pathway and its contribution to emotional impairment and relapse. The goal of these studies is to identify potential mechanisms that can be used as novel pharmacotherapies for treating opioid addiction.

The role of CRF in the antidepressant effects of rapid-acting antidepressants.

The Georgiou Lab will conduct research on the interaction between the brain's stress systems and rapid-acting antidepressants such as ketamine, to investigate combinatorial treatments for treatment-resistant depression. The research will focus on the involvement of corticotropin-releasing factor (CRF) and its projection from the entorhinal cortex (EC) to the hippocampal area CA1 in the antidepressant effects of ketamine. The lab will use in vitro electrophysiology, in vivo fiber photometry and behavioral techniques to study the the mechanisms underlying the CRF-ketamine synergism.