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Dissecting the role of amygdalo-striatal circuits in the regulation of stress and cocaine comorbidity in rats

剖析杏仁核纹状体回路在大鼠应激和可卡因合并症调节中的作用

基本信息

批准号：
10436832
负责人：
Roberto J Morales-Silva
金额：
$ 3.7万
依托单位：
PONCE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436832
关键词：
Address Affect Amygdaloid structure Animal Model Anxiety Disorders Behavior Brain Ceftriaxone Cells Chemosensitization Chronic Chronic stress Cocaine Consumption Corpus striatum structure Cues Development Disease Exhibits Exposure to Extinction (Psychology)Goals Hippocampus (Brain)Individual Intervention Lead Long-Term Potentiation Measures Memory N-Methylaspartate Neurons Nucleus Accumbens Optics Outcome Patients Pharmaceutical Preparations Pharmacological Treatment Play Post-Traumatic Stress Disorders Predisposition Prefrontal Cortex Public Health Rattus Regulation Relapse Research Rodent Role Stress Stressful Event Structure Substance Use Disorder Substance abuse problem Synapses Synaptic Transmission Synaptic plasticity Testing Withdrawal addiction behavior change cocaine exposure cocaine self-administration cocaine use comorbidity drug seeking behavior fear memory in vivo neurophysiology novel therapeutic intervention optogenetics patch clamp preclinical study psychologic reward circuitry traumatic event

项目摘要

SUMMARY/ABSTRACT Generally, post traumatic stress disorder (PTSD) and substance use disorder (SUD) are examined seperately in preclinical studies, although they can occur simultaneously in patients. Therefore, it is necessary to observe these two disorders closely together to better understand the mechanisms that underlie this comorbidity and the effects on the neurophysiology. One of the main problems in addiction is the high relapse rate when the patient is exposed to environmental cues or other factors that can trigger memories associated with addiction. Presently, one of the factors associated with a high relapse state is stress. Exposure to a stressful or traumatic events can lead to the development of PTSD. Moreover, PTSD patients exhibit higher rates of SUD. Two important brain structures involved in the development of these disorders are the basolateral amygdala (BLA) and the nucleus accumbens ( NAc). The BLA concerns the development of fear memories and PTSD, while the NAc is part of the reward circuitry and plays an important role in the progression of SUD. This NAc is sub-divided in two main regions: the core and the shell. Studies have shown that the core drives cocaine-seeking behavior while the shell modulates extinction, decreasing cocaine-seeking behavior. Importantly, the inhibition of BLA-NAc synapses leads to a decrease in overall drug seeking behavior, but the effects of chronic stress on these synapses are still unknown. The objective is to dissect the mechanism by which BLA modulates the NAc in a combined animal model of PTSD and SUD. This will help to better understand how one disorder influences the other. The central hypothesis is that chronic stress will induce neurophysiological changes to the BLA-NAc core and shell synapses, which will correlate with increased cocaine-seeking behaviors. To address this, the team proposed the following aims: Aim 1: Determine the effects of chronic stress on the neurophysiology of synapses of the basolateral amygdala and nucleus accumbens prior to cocaine exposure. Aim 2: Determine the effects of optical activation of BLA-NAc shell and core synapses independently on cocaine-seeking behavior in rats with chronic stress prior to cocaine exposure. The overall goal is to understand how the chronic stress induced neurophysiological changes in a rodent correlate with cocaine seeking-behavior changes prior to cocaine exposure. The long-term goal is to understand the mechanisms and adaptations of the brain caused by a traumatic event that leads to the development of PTSD and the susceptibility of acquiring SUD.

摘要/文摘