Mu-opioid receptors in the habenulo-interpeduncular circuit in opioid dependence

阿片类药物依赖性缰核-脚间回路中的μ阿片受体

• 批准号: 10309782
• 负责人: Thomas Hnasko
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10309782
• 关键词: Acetylcholine; Acute; Affective Symptoms; Animals; Behavior; Behavioral; Biochemical; Brain; CRISPR/Cas technology; Cholinergic Receptors; Chronic; Cocaine; Cocaine Dependence; Data; Dependence; Development; Electrophysiology (science); Future; Glutamate Receptor; Glutamates; Habenula; Ligands; Literature; Maintenance Therapy; Medial; Mediating; Morphine; Morphine Dependence; Mus; Naloxone; Neurons; Neuropeptides; Neurotransmitters; Nicotine; Nicotine Dependence; Opiate Addiction; Opioid; Opioid agonist; Pharmaceutical Preparations; Physiological; Physiology; Play; Process; Public Health; Receptor Activation; Receptor Signaling; Relapse; Research; Role; Signal Transduction; Site; Slice; Synapses; Synaptic Transmission; Testing; Therapeutic; Viral; Withdrawal; Work; addiction; base; behavioral response; cholinergic; drug withdrawal; interpeduncular nucleus; mu opioid receptors; neural circuit; novel therapeutic intervention; novel therapeutics; opioid abuse; opioid withdrawal; optogenetics; physical symptom; receptor; receptor expression; relating to nervous system; response; small molecule; tool; transmission process

PROJECT SUMMARY Withdrawal is a major obstacle in overcoming opioid dependence and addiction. Identifying the neural circuits involved and how opioids modulate their activity is essential for developing new therapeutic strategies. The medial habenula (MHb) expresses particularly high levels of mu-opioid receptor (MOR) and emerging evidence implicates the MHb as a hotspot for the physical and affective symptoms of opioid withdrawal and relapse. Despite this, there is remarkably little information on how MOR signaling influences MHb projection neurons, or how chronic MOR signaling could induce physiological changes in MHb circuits that contribute to withdrawal. MHb neurons project principally to the interpeduncular nucleus (IPN) where they can release acetylcholine (ACh) or glutamate; and some of these neurons can co-release both glutamate and ACh. While cholinergic- and glutamatergic-defined MHb neurons have been implicated in processes underlying addiction, the respective roles and relative importance of these co-transmitters remain unclear. Based on prior literature and preliminary data we posit an important role for glutamate and ACh co-release from MHb to IPN in mediating effects of opioid dependence, including withdrawal. In this exploratory proposal we aim to test how acute and chronic MOR activation influences activity in MHb and synaptic transmission in IPN and contributes to opioid dependence.

项目总结