CONSEQUENCES OF CHRONIC EXPOSURE TO DELTA9-TETRAHYDROCANNABINOL IN MONKEYS

猴子长期接触 Delta9-四氢大麻酚的后果

• 批准号: 7390049
• 负责人: MICHAEL A. TAFFE
• 金额: $ 19.12万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390049
• 关键词: Acute; Address; Adolescent; Affect; Animals; Behavior; Behavioral; Biological Markers; Brain; Cannabinoids; Cannabis; Cerebrospinal Fluid; Chronic; Cognitive; Complement; Complex; Control Groups; Decision Making; Development; Discrimination; Dose; Evaluation; Exposure to; Functional Magnetic Resonance Imaging; Goals; Human; Laboratories; Macaca mulatta; Magnetic Resonance Imaging; Measures; Memory; Modeling; Monitor; Monkeys; Motivation; Motor; Nature; Neurobiology; Neuropsychological Tests; Pattern; Performance; Pharmaceutical Preparations; Physiology; Reversal Learning; Rodent; SR 141716A; Sampling; Short-Term Memory; Specificity; Speed; Staging; Task Performances; Techniques; Testing; Tetrahydrocannabinol; Withdrawal; analog; behavior measurement; cognitive function; cohesion; day; drug withdrawal; executive function; indexing; male; memory recognition; neurobehavioral; neurochemistry; nonhuman primate; research study; translational study; young adult

The objective of Project #3 "Consequences of chronic exposure to A9-tetrahydrocannabinol in monkeys" is to further the goals of the P20 center by establishing a model of adolescent cannabis exposure in nonhuman primates. The studies propose to examine the neurobehavioral and neurochemical sequelae of chronic exposure to A9-tetrahydrocannabinol (THC) in peri-adolescent rhesus monkeys. The model offers a unique translational bridge across the Center Projects because monkeys will be studied across the adolescent (Proj #2) to young adult (Proj #1) developmental stages, will be examined on tasks identical in many cases to the human tasks and can be exposed to specific drug models informed by Proj #4 rodent results. The first Aim is to determine the effects of chronic THC exposure on neuropsychological test battery measures (CANTAB) long established in the laboratory. The acquisition and performance of tasks which measure attentional shift, spatial memory, recognition memory, decision making motor function and motivation will be compared between animals chronically exposed to THC for 2 years and vehicle-exposed monkeys. Since CANTAB measures will also be employed in Proj #1 and #2, and analogous tasks used in the rodent Proj #4, the results from the monkeys will be used to refine the specificity of the behavioral measures for all projects. Periodic cerebrospinal fluid sampling will be employed throughout chronic dosing to monitor neurochemical sequelae of chronic exposure. The second Aim is to determine the effects of withdrawal from chronic THC exposure on behavior, neurochemistry and physiology; antagonist challenge (SR141716A) and spontaneous (28 day) withdrawal approaches will be examined. The fourth Aim is to determine the effects of chronic THC exposure on brain activation using functional Magnetic Resonance Imaging. This f MRI approach is developmental in nature and will be informed by ongoing results from Proj #1 and #2. In total, the studies proposed will address questions regarding the impact of chronic exposure to the primary psychoactive constituent of cannabis and the behavioral specificity, neurochemical and neurovascular sequelae of chronic THC in monkeys will be determined. These studies will also establish a peri-adolescent model of cannabis exposure with tremendous potential for further translational studies in an eventual full Center.

项目3“慢性接触A9-四氢大麻酚的后果， 猴子”是通过建立青少年大麻暴露模型来进一步实现P20中心的目标 在非人类灵长类动物中。这些研究建议检查神经行为和神经化学后遗症， 在青春期前后的恒河猴中长期暴露于Δ 9-四氢大麻酚（THC）。该模型提供了一个 跨中心项目的独特的翻译桥梁，因为猴子将在整个研究 青少年（项目#2）到年轻成人（项目#1）的发展阶段，将在相同的任务中进行检查， 许多情况下，人类的任务，并可能暴露于特定的药物模型所告知的项目#4啮齿动物 结果第一个目的是确定慢性THC暴露对神经心理测试组合的影响 在实验室中长期建立的CANTAB措施。任务的获取和执行， 测量注意力转移，空间记忆，识别记忆，决策运动功能， 将在长期暴露于THC 2年的动物和暴露于车辆的动物之间比较动机 猴子由于CANTAB措施也将用于项目#1和#2， 在啮齿动物项目#4中，来自猴子的结果将用于改进行为的特异性。 所有项目的措施。在整个长期给药期间将定期采集脑脊液样本 来监测慢性接触的神经化学后遗症第二个目标是确定 从长期THC暴露中戒断对行为、神经化学和生理学的影响;拮抗剂激发 将检查（SR 141716 A）和自发（28天）停药方法。第四个目标是 使用功能性磁共振确定长期THC暴露对大脑激活的影响 显像这种f MRI方法本质上是发展性的，将由Proj #1和#2。总的来说，拟议的研究将解决关于长期接触 大麻的主要精神活性成分和行为特异性，神经化学和 将确定猴子中慢性THC的神经血管后遗症。这些研究还将建立一个 青少年期大麻暴露模型具有进一步转化研究的巨大潜力 最后，全中心。