UCLA

For many years, researchers have worked to understand the nuances of behavior, from understanding how the brain fundamentally makes decisions to meet our needs, to how our behavior can become maladaptive, leading us to forgo our basic needs and develop dependence on drugs. Understanding the basic neural systems that underlie reward-related decision making, including how reward-paired stimuli inform reward pursuit decisions, can help clarify what changes occur in the brain following opioid exposure, and how those changes drive drug pursuit and decision making biased towards drugs and away from adaptive rewards. The research presented here discusses potential pathways involved in reward valuation and decision making, and a behavioral model to study decision making between natural and drug rewards. Using pathway-specific chemogenetic inactivation during a memory retrieval task, I have shown that projections between the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) may be critical for using environmental stimuli to make reward value predictions to guide reward behavior. Rats with inactivation of BLA axon terminals in the ACC, and ACC terminals in the BLA, showed deficits in using the recently updated value of one of two food rewards to guide their behavior during an extinction probe test. Further investigation of these pathways using alternative methods, including optogenetic and/or dual viral intersectional chemogenetic approaches, will clarify the roles of these pathways. Pathways involved in reward valuation for adaptive rewards (e.g. food) likely contribute to drug reward valuations and, in turn, contribute to decision making processes that may drive the development of substance dependence. Further, stress and trauma are also known to contribute to substance use disorders. To study how trauma may influence drug-related behavior, I developed a novel food vs. opioid (fentanyl) decision making task to overcome several limitations of canonical drug self-administration studies, combined with stress-enhanced fear learning (SEFL), a well-established rodent model of posttraumatic stress disorder (PTSD). While I did not detect effects of SEFL on opioid behavior, the results suggest several future directions to address the known human PTSD-opioid use disorder comorbidity in preclinical models that can then inform development of behavioral interventions and pharmacotherapies.