PROJECT SUMMARY
Chronic pain is a leading cause of disability worldwide, drastically decreases quality of life, and can drive the
development and maintenance of both alcohol (AUD) and opioid (OUD) use disorders. Both alcohol and opioid
use are reported for pain relief, and co-morbid use of both substances is increasingly common, increasing the
negative effects of either substance used in isolation. Currently, there is limited research, preclinical or clinical,
regarding co-occurring alcohol and opioid use is the context of chronic pain. The kappa opioid receptor (KOR)
and its endogenous ligand dynorphin (DYN) is an endogenous opioid system that is widely expressed throughout
the brain and heavily implicated in alcohol drinking, opioid seeking, and pain chronification. Our lab has recently
identified a novel circuit of nucleus accumbens (NAc) projecting dynorphinergic central amygdala (CeA) neurons
that is modulated by persistent pain and contributes to negative affect. However, this circuit has not been
investigated in alcohol or opioid use. Here, I propose to test the role of DYN CeA-NAc signaling in 1) binge-like
alcohol drinking during persistent pain and protracted fentanyl abstinence, 2) pain avoidance-like behavior and
the effects of alcohol on this behavior, and 3) the effects of binge alcohol on reinstatement of fentanyl seeking
behavior. I will use a combination of behavioral, photometric, and chemogenetic techniques to test the
overarching hypothesis that persistent pain and fentanyl abstinence inhibit a novel dynorphinergic CeA-NAc
circuit to drive binge-like alcohol drinking and subsequent effects on cognitive/motivational pain behaviors and
reinstatement of fentanyl-seeking in a sex-dependent manner. The proposed work will fill a gap in our knowledge
regarding polysubstance use in the context of chronic pain and provide valuable training to a promising young
alcohol neuroscientist.
