Behavioral Core

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Project Summary - Behavioral Core Physical and/or emotional trauma are at the crux of the ongoing pain and opioid epidemics. The complex neural circuitry implicated in pain and opioid misuse challenges our understanding of the underlying pathologies and potential treatments. Cognition and decision-making are certainly impaired in patients with pain. However, the opioids compounds used to treat patients with chronic pain, are themselves also associated with cognitive impairment. Despite the recognition of opioid use disorder (OUD) as a cognitive disorder, the complex neurochemical signaling driving this behavior in cognitive models of OUD remains unclear. We propose a Behavioral Core to synergize the neuro-analytical measurements in Core 3 with the genetically-edited animals in Core 2. This alliance will provide new meaningful insights into the mechanisms of opioid reward and addiction and simultaneously verify new molecular targets and neural pathways underlying OUDs. The Behavioral Core will utilize the DSM-V definition of opioid used disorder (OUD) (i.e., ten major behaviors ranging from inter- and intrapersonal dysfunction to physical and psychological difficulties resulting from increased intake of opioids on a 0-10 scoring system) and apply these to animal behavioral tests to create a similar scoring system for preclinical addiction studies for reliable clinical translational application. These behaviors will be performed in coordination with Cores-2 and Core-3, to provide large data sets optimal for an OUD analysis with bioinformatic and machine learning strategies. In addition, novel molecular targets, therapies and neural networks will be studied to determine to what extent new interventions significantly reduce OUD, in line with the NIH/NIDA mission. The Behavioral Core offer the following pre-established assays: SA1- Establish preclinical models of addictive states that are representative of DSM-V criteria for OUDs. SA2- Establish preclinical models of cognition for evaluation of consequences of opioid exposure. SA3- Integrate OUD behavioral assessment with dynamic neurochemical collection. The escalating number of fatalities from the opioid epidemic necessitates both better interventions to treat OUD and a better understanding of the neural circuits underlying opioid use and addiction. To address this problem, our studies use preclinical animal models based on criteria from human OUD patients. Studies in the Behavioral Core specifically target the circuitry underlying cognitive dysfunction in addictive states that promote poor decision making, drug taking, maintenance and relapse. Our proposed experiments implement multiple technical approaches that will allow for understanding of circuits mediating cognitive aspects of the addictive state. The data generated from the Cores will ultimately lead to hypothesis driven NIH/NIDA research proposals, peer-reviewed publications, national and international presentations and an electronic database system for the scientific community that will speed the discovery of effective therapies for OUD.