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Neural Signatures and Cognitive Performance During Rat Morphine Withdrawal, and Subsequent Impact of Psilocybin

大鼠吗啡戒断期间的神经特征和认知表现，以及赛洛西宾的后续影响

基本信息

批准号：
10748587
负责人：
VICTORIA Ivanova HONES
金额：
$ 4.57万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-16 至 2026-08-15
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10748587
关键词：
Abstinence Adult Affect Alcohol dependence Anhedonia Anxiety Architecture Attenuated Behavior Behavioral Calcium Cells Chronic Cognition Cognitive Cognitive deficits Development Electrophysiology (science)Epithalamic structure Exhibits Feasibility Studies Functional disorder Genetic Transcription HTR2A gene Habenula Human Hyperactivity Image Imaging technology Impaired cognition Impairment Individual Lateral Memory Memory impairment Mental Depression Mental disorders Methods Monitor Morphine Morphine Dependence Naloxone Neurons Nicotine Dependence Opiate Addiction Opioid Opioid replacement therapy Overdose Performance Pharmaceutical Preparations Population Process Psilocybin Psychopathology Rattus Relapse Research Reversal Learning Risk Rodent Rodent Model Role Series Serotonin Agonists Signal Transduction Structure Study models Symptoms System Testing Time Series Analysis Withdrawal addiction behavioral response brain remodeling brain tissue cognitive function cognitive performance cognitive system cognitive task cognitive testing conventional therapy experimental study flexibility imaging modality improved maladaptive behavior mu opioid receptors neural neural circuit neural correlate neuromechanism novel object recognition opioid withdrawal pandemic disease psychiatric symptom receptor receptor expression response serotonin receptor

项目摘要

PROJECT ABSTRACT Opioid addiction is pervasive and widespread, affecting roughly three million U.S. adults. Currently available opioid addiction treatments, such as opioid replacement therapy, fail to slow the growing opioid pandemic and maintain the risk of addiction and overdose. Moreover, available opioid addiction treatments require long-term commitment to treatment with little evidence of long-lasting abstinence. Lastly, opioid replacement therapy is unable to alleviate addiction-induced cognitive impairments. A deeper understanding of the neural and cognitive systems that underlie addiction is necessary for the development of better targeted treatments for opioid addiction. The rodent model of opioid addiction exhibits behavioral markers analogous to those induced in human opioid addiction. Hence, this is a reliable and feasible model for studies of the neural correlates of addiction-related maladaptive behaviors. An emerging body of research suggests that the evolutionarily conserved lateral habenula in rodents is highly implicated in addiction. The lateral habenula is unique in that it directly regulates dopaminergic and serotonergic structures, both of which exhibit dysfunction in addiction. However, with traditional electrophysiological methods of recording lateral habenula neural activity, it has been difficult to clearly assess responses of large populations of neurons. More recent advances in imaging technology have allowed for week-long monitoring of individual neuron calcium dynamics, easing the feasibility of studying the lateral habenula neural responses. Serotonin agonists, such as psilocybin, have shown promising results in reducing the rates of relapse in alcohol and nicotine addiction and improving cognitive function in unhealthy adults. Importantly, lateral habenula hyperactivity is known to drive aversion and is present in withdrawal. Serotonergic agonists have also been shown to quiet lateral habenula activity, suggesting a potential unexplored treatment avenue. Hence, with the use of calcium imaging, I hypothesize that lateral habenula neuron dynamics will shift to a hyperactive state following morphine withdrawal, and that these neural signatures will correlate with decreased performance on cognitive tasks. Additionally, I hypothesize that psilocybin treatment will reinstate baseline lateral habenula activity and improve cognitive performance. The proposed series of experiments will fill the gap in understanding the neural circuitry that drives maladaptive decisions during opiate withdrawal, as well as the behavioral and neural effect of a novel treatment for opiate addiction.

项目摘要