CONSEQUENCES OF CHRONIC EXPOSURE TO DELTA9-TETRAHYDROCANNABINOL IN MONKEYS

项目#3“长期接触A9-四氢大麻酚的后果”的目标是 猴子“是为了通过建立青少年大麻暴露模型来促进P20中心的目标 在非人灵长类动物身上。这些研究建议检查神经行为和神经化学后遗症 青春期恒河猴长期暴露于A9-四氢大麻酚(THC)。该型号提供了一种 独特的横跨中心项目的转换桥梁，因为将通过 青少年(项目2)到青年(项目1)发展阶段，将在相同的任务中进行检查 许多病例需要人工完成任务，并可以接触到特定的药物模型，由Proj#4啮齿动物提供信息 结果。第一个目标是确定长期接触THC对神经心理测试组件的影响 长期建立在实验室中的措施(CANTAB)。任务的获取和执行 测量注意转移、空间记忆、再认记忆、决策运动功能和 长期接触THC 2年的动物和接触车辆的动物之间的动机将进行比较 猴子。由于CANAB措施也将用于项目1和项目2，以及在 啮齿动物项目#4，猴子的结果将被用来提炼行为的特异性 所有项目的措施。在整个慢性给药过程中，将定期采集脑脊液样本 监测慢性暴露的神经化学后遗症。第二个目标是确定 慢性THC暴露对行为、神经化学和生理的影响；拮抗剂挑战 将研究(SR141716A)和自发(28天)戒断方法。第四个目标是 应用功能磁共振技术研究慢性THC暴露对大鼠脑活动的影响 成像。这种核磁共振成像方法本质上是发展的，并将从项目的持续结果中获得信息 #1和#2.总而言之，拟议的研究将解决有关慢性暴露于 大麻的主要精神活性成分及其行为特异性、神经化学和 将确定猴子慢性THC的神经血管后遗症。这些研究还将建立一个 青春期大麻暴露模型具有进一步翻译研究的巨大潜力 最终完全中锋。

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.