UC Irvine

While substance use disorders have been a topic of study in psychology and neurobiologyfor decades, they remain a major problem and only a few effective treatment methods have been developed. The reward, stress, and planning circuits which drive addiction behaviors have been identified and well-studied, uncovering the neurobiological basis for the similarity of addiction behaviors across a variety of substances. Some genetic, developmental, and psychosocial factors which contribute to addiction vulnerability have been identified, but these do not provide sufficient interventional opportunities for treatment or prevention, and do not fully explain the variability in addiction outcomes. Psychological and biological studies of resilience have demonstrated that resilience is an active process, with both overlapping and non-overlapping mechanisms with vulnerability. Here I explore mechanisms of resilience to addiction-like behavior across multiple substances. I use brain activity mapping, pharmacological and viral inhibition and excitation, behavioral measures, immunohistochemical anatomical analysis, and protein

quantification to identify and characterize differences in neuronal activity and circuitanatomy between resilient and susceptible animals. I identify a potential circuit mechanism for negative feedback during drug reward which develops after adolescence, which may contribute to the increased resilience of adult animals to addiction-like behavior compared to juvenile and adolescent animals. A preliminary study suggests that adolescent nicotine or nicotine + ethanol experience does not drive the same cellular response as adolescent high dose amphetamine experience, although similar behavioral outcomes have been observed. I also use a recently developed computational method to identify a population of neurons in the anterior cingulate cortex which both respond strongly to an animal’s first morphine experience and contribute to anxiety during morphine withdrawal. Together, these studies add to the developing literature focused on the compensatory mechanisms involved in resilience to addiction.