Optopharmacology and Sensors for Dissecting Opioid Action In Vivo

用于剖析阿片类药物体内作用的光药理学和传感器

• 批准号: 10040355
• 负责人: Michael R. Bruchas
• 金额: $ 41.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10040355
• 关键词: Absence of pain sensation; Acute; Address; Affect; Animals; Behavior; Biomedical Engineering; Biosensor; Brain; Brain region; Cell membrane; Cells; Cessation of life; Characteristics; Chemicals; Coupled; Detection; Development; Devices; Dimerization; Drug abuse; Endoplasmic Reticulum; Ensure; Fentanyl; Fiber; Fluorescence; Golgi Apparatus; Head; Image; Implant; In Vitro; Infusion procedures; Ligands; Link; Measures; Mediating; Methadone; Methods; Microdialysis; Monitor; Morphine; Motivation; Mus; NIH Program Announcements; Naloxone; National Institute of Drug Abuse; Needles; Neurons; Nucleus Accumbens; Opiate Addiction; Opioid; Opioid Analgesics; Opioid Receptor; Optics; Oral; Overdose; Pathway interactions; Peptide Signal Sequences; Pharmaceutical Preparations; Pharmacology; Photometry; Proteins; Reporter; Research; Resolution; Rewards; Saline; Self Administration; Series; Signal Transduction; Site; System; Testing; Therapeutic Uses; Time; Training; United States; Ventral Tegmental Area; Viral Vector; Wireless Technology; calcium indicator; combinatorial; design; experimental study; extracellular; illicit opioid; in vivo; in vivo imaging; lens; midbrain central gray substance; multidisciplinary; nanobodies; neural circuit; neurotransmission; novel; opioid use disorder; prescription opioid abuse; prescription opioid addiction; prescription opioid misuse; relating to nervous system; response; scaffold; sensor; spatiotemporal; tool; two-photon

PROJECT SUMMARY In 2019, abuse of prescription and illicit opioids resulted in an estimated over 47,000 deaths in the United States. The transition from therapeutic use to destructive opioid use disorder occurs through the maladaptive activation of mesocorticolimbic circuits. Despite decades of research linking these pathways with opioids, surprisingly little is understood about how opioids modulate the brain in vivo in space and time in freely moving animals. This is, in part, driven by the inability to detect and monitor opioids at sub-second timescales. Together, these issues highlight the need for significant advancements for “in vivo precision pharmacology” as indicated specifically in this RFA-DA-20-019 NIDA program announcement. Recent developments using photoactivatable opioid compounds (optopharmacology) together with new optofluidic hardware devices show exciting promise for finally understanding the temporal characteristics of opioid signaling. However, further advances in opioid detection and activation are necessary for fully decoding how opioids modulate neural circuits in vivo. Here we address this challenge head on with a multi-disciplinary team of biochemists, neuroscientists and bioengineers. We will utilize a series of cutting-edge approaches to: 1) develop novel opioid sensors for in vivo, sub-second measures of fentanyl, morphine, and methadone, 2) demonstrate the utility of optopharmacological approaches for dissecting opioid action, and 3) apply the sensors and optopharmacological approaches to perform in vivo precision pharmacological experiments to modulate pain and reward circuits related to drug abuse.

项目总结