The overarching theme of our research program is to understand the contributions of genetic and environmental factors that influence and shape behavior via the involvement of the hypothalamic-pituitary-adrenal (HPA) axis and dopaminergic and noradrenergic systems. I study how behaviors reflective of substance use disorders (e.g., self-administration, conditioned place preference, etc) are affected by stress, sex, and early life manipulations. Indeed, we were one of the first laboratories to incorporate sex as a biological variable in our studies. Another aspect of my research is considered translational as it involves medication development. For example, we are constructing and testing vaccines for methamphetamine abuse and are identifying new pharmacological targets for alcoholism that we test using maintenance and reinstatement of operant responding for alcohol procedures. Broadly, my research program encompasses the areas of motivation, emotion, and learning with a focus on limbic regions, such as the nucleus accumbens and hippocampus, and the neuropharmacological and epigenetic changes that associate with these behaviors.
Research Topic Areas
Early Life Manipulations
- Neonatal isolation – rat pups are isolated from their dam and littermates for 1-h per day on postnatal days 2-9. This manipulation leads to immediate and enduring effects on maternal behavior, stimulant-induced increases in striatal dopamine levels, and enhanced cocaine self-administration.
- Litter gender composition – on postnatal day 1, rat pups are culled and sorted into litters that contain all one sex or are mixed-sex. This manipulation alters maternal behavior and has enduring epigenetic effects such that DNA methylation levels of various genes (Oprm1 which encodes the mu-opioid receptor and N3cr1 which encodes the glucocorticoid receptor) differ in hippocampus and nucleus accumbens.
- Transgenerational effects of paternal alcohol exposure – we are beginning to study how chronic intermittent alcohol exposure in adult male rats affects the behavioral responses to alcohol in their offspring (F1 generation) and ultimately in the grand-offspring (F2 generation). In concert with the behavioral studies, we will be examining candidate epigenetic changes that contribute to behavioral effects seen.
Vaccines for Substance Abuse Disorders (SUD)
- Methamphetamine – conjugate vaccines constructed against methamphetamine alter the locomotor and conditioned rewarding effects of methamphetamine in mice. We are currently testing if the vaccine blocks reinstatement of extinguished responding for methamphetamine in rats.
- Nicotine – a conjugate vaccine constructed against nicotine is being developed and will be tested initially for it ability to alter nicotine effects on locomotor acticity in mice.
Medication Development for Alcohol Use Disorders (AUD)
- Fenofibrate – this peroxisome proliferator-activator receptor alpha agonist decreases maintenance of operant responding for alcohol.
- Sex-dependent effects of naltrexone – this mu opioid antagonist decreases appetitive behaviors in female rats and consummatory behaviors in male rats.
- Kappa antagonist for co-morbidity of PTSD and alcohol – we will examine the ability of a kappa antagonist to decrease the enhanced self-administration of alcohol in rats subjected to an animal model of Post-traumatic Stress Disorder (PTSD).
We are assessing substance-induced alterations in the microbiome with the aim to test possible treatments that target the gut microbiota for relapse and withdrawal.