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PET Imaging of Cortical Dopamine Transmission in Cocaine Addiction

可卡因成瘾过程中皮质多巴胺传输的 PET 成像

基本信息

批准号：
9193064
负责人：
RAJESH NARENDRAN
金额：
$ 56.17万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9193064
关键词：
Abstinence Addictive Behavior Affinity Age Agonist Amphetamines Amygdaloid structure Anxiety Attention Award Binding Brain Chronic Chronic Disease Clinical Research Cocaine Cocaine Dependence Cognition Cognitive deficits Conflict (Psychology)Corpus striatum structure Corticotropin-Releasing Hormone Decision Making Detection Development Dopamine Dynorphins Female Functional Imaging Funding Gender Human Image Impaired cognition Intoxication Investigation Knowledge Lead Ligands Measurement Measures Mediating Memory Midbrain structure Motor Negative Reinforcements Neurocognitive Deficit Neuropeptides Neurotransmitters Nociception Noise Opioid Peptide Oral Outcome Measure Pathologic Peptide Receptor Peptides Pharmaceutical Preparations Phase Positive Reinforcements Positron-Emission Tomography Preclinical Drug Evaluation Prefrontal Cortex Raclopride Relapse Risk Rodent Rodent Model Role Sampling Scanning Short-Term Memory Signal Transduction Smoking Status Standardization Stress System Time Up-Regulation Urine Validation Vasopressins Ventral Striatum Withdrawal addiction cocaine exposure cognitive function contingency management craving endogenous opioids experimental study follow-up hypocretin imaging study in vivo interest neurochemistry neuropeptide Y nociceptin novel preference prevent processing speed public health relevance radiotracer receptor relapse prediction response transmission process

项目摘要

DESCRIPTION (provided by applicant): Three different imaging groups have demonstrated a blunting in stimulant induced dopamine release at the level of the striatum in cocaine dependent subjects. An important limitation of these studies is the fact that measurements of D2/3 receptors and amphetamine-induced dopamine release were restricted mostly to the striatum because the ligands used did not provide enough signal to noise ratio to quantify D2/3 receptors in extrastriatal regions. Given that functional imaging studies in cocaine dependence suggests a relationship between pathological activation of the prefrontal cortex (PFC) and cognitive deficits it is of extreme interest to understand the regulatory role of dopamine in this particular region. During the previous cycle of this award we validated the use of the high affinity dopamine D2/3 radiotracer [11C]FLB 457 to measure amphetamine-induced dopamine release in the PFC. In aim 1 we propose to use this recently validated imaging paradigm in a clinical study in cocaine dependence to characterize amphetamine-induced dopamine release in the PFC, and relate it to cognitive deficits and relapse. We hypothesize that amphetamine-induced dopamine release will be decreased in the mesocortical dopaminergic system in cocaine abusers relative to healthy comparison subjects and be associated with cognitive impairments and less time to relapse. Recent basic investigations postulate that an imbalance between neurotransmitters that regulate stress and anti-stress underlie negative reinforcement and relapse in addiction. Nociceptin (N/OFQ) is one such peptide neurotransmitter that exerts anti-stress effects and prevents relapse in rodent models of addiction. No previous human studies have characterized N/OFQ in addiction. In aim 2, we propose to use [11C]NOP-1A PET to measure the in vivo status of nociceptive opioid peptide (NOP) receptors in cocaine abusers, and evaluate its relationship with stress, anxiety, craving, and relapse. This aim marks a cautious first step in a new direction for this renewal application, which we intend to follow up with further experiments in cocaine dependence as novel radiotracers become available to image other components of the brain stress (e.g., corticotrophin releasing hormone, orexin, vasopressin, etc.,) and anti-stress system (neuropeptide Y).