Ovarian Sex Steroid Hormones and Drug Addiction During Pregnancy: Although drug addiction affects both sexes, there is evidence that this disorder develops and progresses differently in males vs. females. One factor that may underlie these sex differences is the differential exposure to sex steroid hormones across the two sexes. Indeed, a growing body of literature suggests that responses to drugs of abuse in females is strongly influenced by levels of estrogen and progesterone. Although levels of these hormones change dramatically during pregnancy, few studies to date have examined how ovarian sex steroid hormones influence drug addiction during pregnancy. Consequently, this project focuses on the extent to which estradiol and progesterone signaling within the brain impacts motivation for cocaine during pregnancy in rats.
Ovarian Sex Steroid Hormones and Socio-Cognitive Functioning in Early-Onset Alzheimer’s Disease: Alzheimer’s disease (AD) is characterized by neurotoxic pathology (e.g., amyloid beta (Aβ) plaques and phosphorylated tau protein tangles) as well as progressive loss of socio-cognitive functioning. A subset of individuals (5-10%) with AD are diagnosed prior to the age of 65; this is known as early-onset Alzheimer’s Disease (EOAD). In females, the timing of EOAD typically corresponds with a dramatic decline of estradiol levels due to the onset of menopause; importantly, even in otherwise healthy individuals this loss of estradiol is associated with some socio-cognitive deficits due to estradiol’s normal facilitative role in supporting these functions. There is some thought that estradiol signaling at its receptors in the hippocampus (an important brain area for socio-cognitive functioning) can enhance Aβ degradation via induction of neprilysin (NEP), an enzyme responsible for clearance of Aβ proteins. Our current project seeks to determine whether estrogen replacement therapy positively impacts socio-cognitive functioning in a female rat model of EOAD via upregulation of NEP in the hippocampus.
Sex Differences in Behavioral Responses to Cocaine in a Rat Model of Attention-Deficit/Hyperactivity Disorder: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects approximately 4.5 million individuals in the US. ADHD is characterized by hyperactivity, the inability to maintain focus, and difficulty controlling impulsivity. Substance use disorders (SUDs) are highly prevalent among adult individuals with ADHD, with some studies estimating as high as 11.5%. Initiating drug use in adolescence is associated with higher odds of developing a SUD later in life, and the overwhelming majority of individuals in treatment for SUDs initiated their drug use during adolescence. This project uses a genetic, adolescent rat model of ADHD to examine the extent to which individuals with ADHD are more sensitive to the neurobehavioral effects of cocaine.
Metabolic Therapies and Drug Addiction: This project focuses on the effects of a ketogenic diet on behavioral responses to drugs of abuse. The ketogenic diet is a high fat, low carbohydrate and adequate protein diet that has shown therapeutic potential in disease states and disorders as diverse as epilepsy, autism, schizophrenia, Alzheimer’s, and Parkinson’s. Although the specific mechanisms of action for this diet remain to be fully elucidated, its positive impacts on energy metabolism and neuroinflammation suggest that it may also be an effective therapy for drug addiction. Studies in rats are currently underway to determine if this is indeed the case.