Past SCORE Pilot Projects


Pharmacotherapy for adolescent alcohol use: Investigating sex differences in cue-reactivity and neuroinflammation

ReJoyce Green, Ph.D.

Sex differences in alcohol use and alcohol-related consequences may substantially impact treatment outcomes. The pilot project will utilize data from a recently completed adolescent pharmacotherapy trial examining neural response to a novel pharmacotherapy, N-acetylcysteine (NAC), for adolescent alcohol use. The project will examine two novel treatment outcomes, reactivity to alcohol cues and markers of neuroinflammation, to test whether females respond more favorably to NAC. Results from the pilot project will address a critical gap in the literature of how sex may alter response to pharmacotherapy for alcohol use among adolescents.

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.

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.

Sex-specific role of perineuronal nets in chronic METH-induced hypofrontality and cognitive deficits

Ahlem Assali, Ph.D.

Due to the exclusion of females from research and clinical studies in the past, multiple drugs used in females were inefficient or over-dosed, compared to males. This pilot project is investigating perineuronal nets(PNNs)-related mechanisms underlying methamphetamine (METH)-induced hypofrontality and cognitive deficits in both males and females. Despite the fact that females may not display an increase in PNNs density in response to chronic METH, and since PNNs formation has been linked to increased PV+FSI activity, the hypothesis that diluted ChABC to slightly digest PNNs in the female PFC could induce a partial rescue of METH-induced cognitive deficits and hypofrontality in female rats is being tested

T-cell regulation of cardiac physiology and cognitive decline in women

Kristine DeLeon-Pennell, Ph.D. 

Post-menopausal women have a two-times higher risk of developing cardiovascular disease compared to pre-menopausal women. For women who have a heart attack (myocardial infarction or MI), there is a twofold higher chance of decline in cognitive function. The goal of this SCORE pilot project is to understand how hormonal regulation of CD8 T-cells regulate the wound healing response after MI and can promote impaired cognitive decline. The central hypothesis is that CD8 T-cells are direct and indirect regulators of cognitive decline after MI through hormonal mechanisms. This is the first proposal to integrate multidisciplinary approaches to evaluate hormonal regulation of CD8 T-cells in the MI setting, and will add to the understanding of critical mechanisms underlying adverse effects of the adaptive immune response in cognitive function after MI.

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.  

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. 

Investigating neural and microbiome sex differences in adolescent alcohol use

Anna Kirkland, Ph.D.

This pilot project is investigating potential neural and microbiome sex differences within binge drinking adolescents as compared to non-drinking controls. The project is building upon baseline data collected from an on-going adolescent alcohol pharmacotherapy trial (K23 AA025399) by adding a control group to analyze the sex-specific effects of heavy alcohol use. This work is significant for the adolescent alcohol use disorder (AUD) field because it will help to 1) understand SABV related neural and microbiome alterations due to heavy alcohol use, and 2) to help identify potential high-yield pharmacological treatment targets for adolescents with AUD.

Endocannabinoid dysregulation in cannabis dependence and acute cannabis withdrawal

Erin Martin, Ph.D. candidate

Endocannabinoids regulate several key homeostatic processes (e.g. eating, sleep, mood) that are negatively impacted in cannabis withdrawal, particularly in women. With this pilot project, we look to examine the effects of heavy cannabis use and acute cannabis withdrawal on peripheral endocannabinoid levels in both sexes, and to determine if the degree of change in endocannabinoid levels during withdrawal vs. heavy use is associated with severity of cannabis withdrawal symptom expression. Outcomes from this project can then be used to inform sex-specific pharmacotherapeutic strategies for cannabis use disorder.   

Sex specific differences in cross-sensitization between THC and heroin seeking and withdrawal

Daniela Neuhofer, Ph.D.

The current opioid epidemic highlights the need for alternative pain treatment strategies and cannabis is becoming widely legalized for medical use, including pain management. Cannabis could serve as a partial therapeutic alternative to opioids but it is not clear whether a history of chronic THC increases the risk of developing of opioid use disorder (OUD). This pilot project is utilizing a rodent model to systematically investigate 1) whether a history of THC self-administration modulates different stages of heroin intake, withdrawal and craving, 2) whether these effects of THC pre-exposure are sex-specific and 3) neuroadaptations in brain regions involved in OUD.

Establishing a role for Arc as a molecular mechanism of sex differences in anxiety-like behavior

Rachel Penrod-Martin, Ph.D.

Anxiety disorders are the most common mood disorders, and are experienced by females at higher rates than males.  While there are many pre-clinical studies of anxiety, few of them focus on the underlying neurobiology that may drive sex differences in anxiety. The SCORE pilot project grant supports Dr. Penrod-Martin's experiments to characterize sex-specific patterns of brain activation produced by anxiety experience, a key step in understanding if there are sex-differences in how the brain processes and responds to anxiety. These findings will help focus attention to the brain regions most likely to be driving anxiety in the two sexes. Another aspect of this project is to understand how sex hormones (estrogen, progesterone) influence anxiety behavior, brain activation, and the expression of proteins in the brain that serve as the connection between brain activity and behavior. These findings will help determine if there are sex-specific mechanisms regulating anxiety and help target those mechanisms to improve anxiety symptoms.

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.