Current Pilot Projects

Sex differences in stress-induced ethanol self administration in C57/BL6J mice

Anny Gano, Ph.D. & Courtney King, Ph.D.

This project uses a novel preclinical model to examine sex differences in stress-induced relapse behavior. This model introduces an alternative to typical reinstatement protocols by assessing both craving-like ("seeking") responses as well as stress-driven alcohol consumption, which may offer excellent face, constructive, and predictive validity to relapse behavior seen in individuals with alcohol use disorder.  Additionally, a growing literature suggests that the ovarian hormone progesterone, which fluctuates naturally during the menstrual cycle in females, may play a key role in sex differences observed in stress reactivity and substance use. These effects can be mediated by the progesterone metabolite allopregnanolone (ALLO). This work also examines potential sex differences in the relationship between levels of neuroactive steroid ALLO and stress-induced relapse behavior. 

Initial intervention efficacy, cortisol and oxytocin among pregnant women with PTSD 

Mary Shapiro, Ph.D.

This project aims to adapt and test a brief computer-assisted intervention (psychoeducation + skills) for pregnant women with elevated PTSD symptoms. In this open trial pilot study, 20 pregnant women in their first trimester will be invited to participate if they endorse elevated PTSD symptoms. Oxytocin and cortisol will be measured at baseline, one month post-intervention, three months post-intervention, and post-delivery to inform the relationship between these hormones, PTSD symptoms, and peripartum/postpartum outcomes. In addition to receiving the psychoeducation and skills intervention during their first trimester, women will be offered a “booster session” intervention following delivery to enhance utilization of skills during a critical period for maternal mental and physical health outcomes. 

Sex-associated difference in mitochondrial stress response following traumatic brain injury

Onder Albayram, Ph.D.

Traumatic brain injury (TBI) is a leading cause of disability and mortality, resulting in over 3 million TBI related hospital visits in the US and 80,000 deaths each year.  An increasing number of studies demonstrate significant sex differences in response to TBI, with females exhibiting more resistance to secondary injuries and better outcomes in comparison to their male counterparts. Dysfunctional mitochondrial stress response/mitophagy is a major driver of the secondary deleterious cascades following brain injury. Accumulating evidence suggests that propensity of mitophagy may vary between males and females, particularly in conditions of cellular stress such as TBI. However, it still unknown how sex differences in mitochondrial dynamics and mitophagy contribute to the development of disease progression in TBI. This pilot project is testing the central hypothesis that sex-specific differences in mitochondrial stress response may contribute to sexual dimorphism in TBI outcomes.

Sex, opiates, & prefrontal cortex: Progestin suppression of relapse to opiate seeking in females

Elizabeth Doncheck, Ph.D.

There are currently few effective treatments that can prevent relapse in opioid use disorder (OUD).  This is especially alarming for women as clinical observations imply that females are more vulnerable to relapse than their male counterparts.  However, relapse vulnerability in females co-varies with the ovarian hormone cycle such that peak levels of progesterone and, more specifically, its metabolite allopregnanolone appear to confer protection against relapse.  The goal of this pilot project is to identify treatment targets by determining the underlying mechanisms whereby allopregnanolone provides protection against relapse in women with OUD.  Using state-of-the-art preclinical techniques such as two-photon microscopy, how allopregnanolone regulates the neural circuitry that governs relapse behaviors is being investigated.  

The role of estrogens in the cognitive deficits resulting from methamphetamine use

Monserrat Armenta-Resendiz, Ph.D.

Addiction to methamphetamine (METH) is a serious health problem that involves significant impairments in cognitive and executive functions. Females and males differ in their response to METH use. However, there is a gap of knowledge regarding the differences associated with gender in cognitive processes and executive functions following repeated METH administration. Using electrophysiological recordings ex vivo and behavioral tasks in rats, the hypothesis that estrogens decrease dopamine concentration in the PFC, thus having a neuroprotective role ameliorating the cognitive deficits, sensitization and PFC hypoactivity produced by repeated METH administration, will be tested.