Marijuana & Cytokine Actions on Rat Brain Mitogenesis

描述（由申请人提供）： 慢性药物滥用的一个常见结果是认知丧失或功能障碍。在许多这些情况下，没有明确的神经病理学与这些缺陷。一个恰当的例子是大麻素药物，大麻，其使用通常与急性和慢性中毒后的记忆丧失有关。然而，没有任何明确的证据表明与其使用相关的坦率的神经病理学（参见。毒品“摇头丸”3，4-MDMA）。 最近的证据表明，哺乳动物的大脑（包括人类）继续产生新的神经元，直到成年。此外，这一过程在新的学习和记忆中也很重要。该申请提出了研究，其检查δ-四氢大麻酚（THC）对成年大鼠齿状回（DG）中的有丝分裂（细胞增殖）（神经发生的第一阶段）的影响。这些影响也将在其与促炎细胞因子白细胞介素-1 β（IL-1 β）相互作用的背景下进行研究，IL-1 β在各种感染和应激条件下释放。 THC将以三个剂量急性和慢性腹膜内施用。 此外，这些动物中的一些还将长期给予IL-1 β。在这些不同的药物处理（或对照处理）之后，所有动物将被施用溴脱氧尿苷（BrdU）并在两小时后被处死。将对动物进行灌注，取出其大脑并进行BrdU免疫反应性处理。将使用光学显微镜对DG的颗粒细胞层和门中的BrdU标记细胞进行定量。 据推测，慢性，可能是急性，THC将抑制DG有丝分裂，应激相关的细胞因子IL-1 β也将具有这种作用。进一步假设这两种化合物的作用在抑制DG有丝分裂中至少是相加的。

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.