Marijuana & Cytokine Actions on Rat Brain Mitogenesis

大麻

• 批准号: 6695418
• 负责人: BARRY L JACOBS
• 金额: $ 7.9万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-25 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695418
• 关键词: Cannabis; brain; cell proliferation; cognition; dentate gyrus; immunocytochemistry; interleukin 1; laboratory rat; marijuana abuse; memory; neurons; stress

DESCRIPTION (provided by applicant): A common result of chronic drug abuse is cognitive loss or dysfunction. In many of these cases no definitive neuropathology is associated with these deficits. A case in point is the cannabinoid drug, marijuana, whose use is most often associated with memory loss, following both acute and chronic intoxication. There is not, however, any definitive evidence of frank neuropathology associated with its use (cf. the drug "ecstasy" 3,4-MDMA). Recent evidence indicates that the mammalian brain (including humans) continues to produce new neurons into adulthood. Additionally, this process has been shown to be important in new learning and memory. This application proposes research which examines the effects of the delta-tetrahydrocannabinol (THC) on mitogenesis (cell proliferation), the first phase of neurogenesis, in the dentate gyrus (DG) of adult rats. These effects will also be studied in the context of their interaction with the proinflammatory cytokine interleukin-1beta (IL-1beta), which is released under a variety of infectious and stressful conditions. THC will be administered intraperitoneally both acutely and chronically in three doses. In addition, some of these animals will also be given IL-1beta chronically. Following these various drug treatments (or control treatments), all animals will be administered bromodeoxyuridine (BrdU) and sacrificed two hours later. The animals will be perfused and their brains removed and processed for BrdU-immunoreactivity. BrdU-labeled cells in the granule cell layer and hilus of the DG will be quantified using light microscopy. It is hypothesized that chronic, and possibly acute, THC will suppress DG mitogenesis and that the stress-related cytokine IL- 1beta will also have this effect. It is further hypothesized that the actions of the two compounds will be at least additive in suppressing DG mitogenesis.

描述（由申请人提供）： 慢性药物滥用的常见结果是认知丧失或功能障碍。在许多情况下，这些缺陷都没有明确的神经病理学。一个很好的例子是大麻素药物大麻，其用途通常与记忆丧失有关，均在急性和慢性中毒之后。但是，没有任何与其使用相关的坦率神经病理学的确切证据（参见药物“摇头丸” 3,4-MDMA）。 最近的证据表明，哺乳动物的大脑（包括人）继续产生新的神经元成年。此外，此过程已被证明在新的学习和记忆中很重要。该应用提出了研究，研究了成年大鼠的齿状回（DG）中，研究三氢核（THC）对有丝分裂发生（细胞增殖）的影响（细胞增殖）。这些效果还将在与促炎性细胞因子白介素1Beta（IL-1Beta）相互作用的背景下进行研究，该效果在各种传染性和压力条件下释放。 THC将以三剂急性和慢性地进行腹膜内施用。 此外，其中一些动物还将长期给予IL-1Beta。遵循这些各种药物治疗（或对照治疗），所有动物将被施用溴脱氧尿苷（BRDU），并在两个小时后处死。这些动物将被灌注，并去除并加工其大脑以进行BRDU免疫反应性。将使用光学显微镜对颗粒细胞层中的Brdu标记细胞和DG的Hilus进行定量。 假设慢性且可能急性的THC会抑制DG有丝分裂发生，并且与应力相关的细胞因子IL-1Beta也将具有这种作用。进一步假设，两种化合物的作用至少在抑制DG有丝分裂发生方面是加性的。