Neuroinflammation, Glutamatergic Signaling, and Nicotine Addiction

Neuroinflammation occurs with chronic drug use and has been implicated across a number of neuropsychiatric and neurodegenerative pathologies. We examine markers for neuroinflammation after nicotine addiction, during withdrawal, and during nicotine relapse. Further, we utilize a cre-recombinase driver transgenic rat line to chemogenetically activate or inhibit microglia, and examine their impact on nicotine neurobiology and behavior. Additionally, we evaluate causal relations between noninflammatory signals and rapid, transient, cue-induced synaptic plasticity in a nicotine addiction model. Due to the crucial roles glial cells have in these relations, analysis of microglial and astroglial cytokine production, morphology, and receptor expression is used to develop potential pharmocotherapeutic targets for nicotine addiction.

Steroidal Hormone Effects on Nicotine Addiction Vulnerability in Females

Women are typically more vulnerable to substance use disorders and clinical trials have shown that long-term smoking cessation is more difficult to achieve in women than men. Clinical research studies suggest that the menstrual cycle phase in women can affect cigarette craving and propensity to relapse to smoking following abstinence. Our lab explores hormonal influences on glutamatergic and neuroimmune signaling mechanisms in addiction. Our investigations of hormonal involvement in the pathways that underlie drug-seeking behaviors will help inform the direction of future clinical research in the treatment of smoking.

Mechanisms of Opioid and Cocaine Polysubstance Addiction

Opioid use disorder (OUD) is a leading public health crisis in the United States that has led to a decrease in life expectancy. Individuals with OUD often use other substances, including cocaine. Stimulant use during opioid withdrawal may represent an attempt to ameliorate opioid withdrawal effects, but combined use of cocaine with opioids increases overdose risk. Results from previous studies in our lab illustrate glutamate as a conserved neural mechanism underlying drug-motivation in both opioid and cocaine use, as well as in polysubstance use. Our current research aims to develop targets for ameliorating glutamate dysregulation observed in comorbid addiction of these substances.

Mapping the Neural Circuity of Nicotine Addiction

Research funded by a R21 awarded by the NIDA examines the role of cholinergic interneurons within the nucleus accumbens in nicotine seeking motivation. Using specific chemogenic modulation of accumbens neuronal signaling in transgenic rats, we examine the link between signaling of different cell types to better our understanding of neural circuity underlying addiction-related behaviors. Further, we are interested in glutamatergic mechanisms, particularly how the disruption of glutamate homeostasis occurs in the drug-experienced brain. The resulting alteration of AMPA and NMDA receptor expression, affecting synaptic plasticity and neural communication, is also researched in our lab.