Drugs of abuse drive transmitter switching that causes drug-induced behavior

滥用药物会驱动发射器切换，从而导致药物诱发的行为

基本信息

批准号：
9766809
负责人：
NICHOLAS CANADAY SPITZER
金额：
$ 23.63万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9766809
关键词：
Addictive Behavior Address Adult Affect Alcohol or Other Drugs use Animal Behavior Behavior Behavioral Brain Brain region Cells Chronic Cognitive deficits Data Development Drug usage Exposure to Extinction (Psychology)Glutamates Impaired cognition Intake Intervention Knowledge Lead Link Maintenance Methamphetamine Molecular Target Monoamine Oxidase Morale Mus N-Methyl-D-Aspartate Receptors Neuronal Plasticity Neurons Neurotransmitters Pharmaceutical Preparations Pharmacology Phencyclidine Play Prefrontal Cortex Process Psychological reinforcement Relapse Rewards Role Stimulus Substance of Abuse Synapses System Testing Time addiction behavioral sensitization cognitive function compulsion drug induced behavior drug of abuse experimental study functional disability human subject negative emotional state neurochemistry neurotransmission novel preference prevent response vesicular monoamine transporter

项目摘要

Project Summary Abstract: Repeated exposure to a drug of abuse can lead to the development of an addiction, a chronic and relapsing illness that has been defined as the compulsion to seek and take the drug, the loss of control in limiting intake, and the emergence of a negative emotional state. The transition from drug intake to addiction involves neuroplasticity of brain circuits related to reward, impulse control and affect. One of the brain regions that is functionally impaired by drug intake is the prefrontal cortex (PFC), in which drugs of abuse induce alterations in activity that seem to be crucially involved in the loss of control over drug intake. Increasing our knowledge of the ways in which drugs of abuse impact these circuits is important to better understand the mechanisms underlying the transition to addiction and to allow the development of novel interventions and treatment. The proper function of brain circuits relies on the correct specification and orchestration of neurotransmission. Accumulating evidence has recently established that when prolonged environmental stimuli produce a sustained alteration in the electrical activity of a subset of neurons, these neurons can undergo a respecification of the neurotransmitter they express, often resulting in a switch from an excitatory to an inhibitory transmitter or vice versa. This newly appreciated form of neuroplasticity, called neurotransmitter switching, has been repeatedly observed in the adult mammalian brain and associated with alterations in animal behavior. We hypothesize that repeated exposure to drugs of abuse can induce neurotransmitter switching that in turn contributes to the establishment of drug-induced behavioral alterations such as cognitive deficits, behavioral sensitization and drug-induced reinforcement. Two specific aims will test this hypothesis. The 1st specific aim will test whether sub-chronic treatment with PCP or METH induces neurotransmitter switching in the PFC. The 2nd specific aim will determine whether there is a causal link between neurotransmitter switching and drug- induced behavioral alterations including cognitive deficits, behavioral sensitization, and drug-induced reinforcement.

项目摘要摘要：反复接触滥用药物会导致成瘾的发展，慢性和复发被定义为寻求和服用药物的强迫性的疾病，失去控制限制摄入量的疾病，以及负面情绪状态的出现。从药物摄入到成瘾的过渡涉及与奖励，冲动控制和影响有关的脑回路的神经塑性。大脑区域之一药物摄入功能受损的是前额叶皮层（PFC），其中滥用药物会导致改变似乎至关重要的是失去对药物摄入的控制。提高我们对滥用药物影响这些电路的方式对于更好地了解机制很重要基于成瘾的过渡并允许发展新的干预措施和治疗。大脑电路的正确功能依赖于神经传递的正确规范和编排。累积的证据最近确定，延长的环境刺激会产生神经元子集的电活动的持续改变，这些神经元可以接受它们表达的神经递质的解释，通常导致从兴奋剂转变为抑制发射器，反之亦然。这种新的神经塑性形式，称为神经递质切换，在成年哺乳动物大脑中反复观察到动物行为。我们假设反复接触滥用药物会引起神经递质的转换有助于建立药物引起的行为改变，例如认知缺陷，行为敏化和药物引起的加固。两个具体的目标将检验这一假设。第一个特定目标将测试使用PCP或METH的亚少生处理是否诱导PFC中的神经递质切换。这第二个特定目标将决定神经递质切换与药物之间是否存在因果关系引起的行为改变，包括认知缺陷，行为敏感和药物诱导加强。