Neuronal Plasticity in the BNST and Alcohol Dependence

BNST 和酒精依赖中的神经元可塑性

基本信息

批准号：
7799675
负责人：
WALTER G FRANCESCONI
金额：
$ 33.77万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-15 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7799675
关键词：
Abstinence Acute Address Affective Alcohol consumption Alcohol dependence Alcohols Aminobutyric Acids Amygdaloid structure Animals Area Arousal CRF receptor type 1 Calcium Cations Cell Nucleus Chronic Cocaine Corticotropin-Releasing Hormone Cyclic Nucleotides Disease Drug Addiction Drug Controls Drug abuse Drug usage Emotional Ethanol dependence Feedback Frequencies Heroin Impairment In Vitro Individual Intake Lateral Long-Term Effects Long-Term Potentiation Mediating Negative Reinforcements Neurobiology Neuronal Plasticity Neurons Peptides Pharmaceutical Preparations Property Psychological reinforcement Rattus Recording of previous events Relapse Role Slice Source Stress Structure Structure of terminal stria nuclei of preoptic region Synaptic plasticity System Voltage-Gated Potassium Channel Withdrawal alcohol seeking behavior base biological adaptation to stress drinking drug of abuse effective therapy heuristics negative emotional state neuronal excitability response stria terminalis

项目摘要

DESCRIPTION (provided by applicant): Changes in neuronal excitability and synaptic plasticity are increasingly recognized as cellular substrates of the long-term effects of drugs of abuse. The lateral subdivision of the bed nucleus of the stria terminalis (BNST) is involved in stress responses and in the long-lasting motivational dysregulation associated with drug dependence. We observed that high frequency stimulation (HFS) of the area of the stria terminalis in BNST slices in vitro induced a long term potentiation (LTP) of intrinsic excitability and a persistent increase in the temporal precision of firing of neurons in the juxtacapsular subdivision of the lateral BNST (jcBNST). Induction of this form of neuronal plasticity in the jcBNST was impaired during protracted withdrawal in rats with a history of dependent intake of alcohol, cocaine or heroin. In this application we propose to investigate the induction mechanisms of LTP of intrinsic excitability and temporal fidelity of jcBNST neurons in ethanol dependent rats. The impaired plasticity of the jcBNST described here could be relevant to the emotional dysregulation long hypothesized to underlie the transition to compulsive drug taking in dependent individuals. To address this hypothesis, it is proposed to investigate if treatments that have been shown to reduce increased drinking in dependent rats and reinstatement of alcohol-seeking behavior restore LTP of intrinsic excitability and temporal fidelity of jcBNST neurons in ethanol dependent rats. The elucidation of the mechanisms behind the changes in the jcBNST in animals with a history of alcohol dependence is likely to have heuristic value for the understanding of the neurobiological bases of drugs of abuse.

描述（由申请人提供）：神经元兴奋性和突触可塑性的变化越来越被认为是滥用药物长期影响的细胞底物。 Stria末端（BNST）的床核的横向细分参与压力反应以及与药物依赖性相关的持久动机失调。我们观察到，BNST片段中质末端的高频刺激（HFS）在体外诱导了内在兴奋性的长期增强（LTP），并持续提高神经元在近期BNST（JCBNST）近后细胞中神经元的放电的时间精度。在大鼠的持续戒断中诱导这种形式的神经元可塑性在大鼠的长时间戒断中受到损害，患有酒精，可卡因或海洛因的病史。在此应用中，我们建议研究JCBNST神经元在乙醇依赖大鼠中的内在兴奋性和时间忠诚度的LTP的诱导机制。此处描述的JCBNST的可塑性受损可能与长期假设的情绪失调有关，这是为了过渡到接受依赖人的强迫性药物的基础。为了解决这一假设，建议研究是否已证明已显示依赖大鼠的饮酒的治疗是否恢复了乙醇依赖大鼠的JCBNST神经元的内在兴奋性和时间延迟的LTP。阐明具有酒精依赖史的动物中JCBNST变化背后的机制可能具有启发式价值，以理解滥用药物的神经生物学基础。