CANNABINOIDS IN DOPAMINE NEURON ELECTROPHYSIOLOGY

每月约有1000万人吸食大麻或更多 经常使用，使其成为最常用的非法药物。第12届的2% 评分员每天都会使用大麻。此外，大麻的使用量甚至 1992年，较年轻的学生(8名年级学生)增加了整整一个百分点。 2000年的健康人将大麻的使用作为第一年龄的典型- 一种使用现象，即在15岁之前使用该词与更大程度的滥用有关 以及15岁以后的其他药物。这些事实加上知识 具有精神活性的大麻素会产生无数的行为影响 通过在以下方面的行动改变CNS内的信息处理 内源性大麻素受体需要做出实质性的努力 使其了解其对中枢神经系统功能的影响。这个 这些研究的总体目标是确定黄连的作用机制(S) 精神活性大麻素，三角洲-9-四氢大麻酚(Delta-9-THC) 那些含有多巴胺的系统被认为是参与 滥用药物的强化和精神分裂特性。 具体地说，急性和长期服用Delta-9的影响- THC和内源性脑组织成分双胺对中脑多巴胺的影响 神经元(A9和A10)被选作研究对象。在建议的 实验中，我们将使用单个神经元细胞外记录来确定 不同种类的大麻素(精神活性和非精神活性)对 动作电位产生的速度和模式，更重要的是 长期暴露于Delta-9-THC对这些参数的影响。在……里面 此外，体外中脑神经元的细胞内记录 切片准备将用于分析急性和慢性的影响 Delta-9-THC对神经细胞膜特性和神经元膜电位的影响 兴奋性。这些项目应该使我们能够描述 Delta9-THC暴露对中脑多巴胺神经生理学的影响。 从这些实验中得出的数据将提供相关信息 Delta9-THC对这些多巴胺神经元的药理作用 牵涉到情绪、认知和感觉运动的变化 吸食大麻。

Approximately 10 million persons a=use marijuana on a monthly or more frequent basis making it the most commonly used illicit drug. 2% of 12th graders use marijuana on a daily basis. Moreover, marijuana use at even younger ages (eight graders) increased a full percentage point in 1992. Healthy People 2000 refers to marijuana use as typifying the age-at-first- use phenomenon whereby its use prior to age 15 relates to its greater abuse and that of other drugs after 15. These facts coupled with the knowledge that psychoactive cannabinoids produce a myriad of behavioral effects and alterations in information processing within the CNS through actions at endogenous cannabinoid receptors requires that substantial efforts should be made to understand its effects on central nervous system function. The overall goal of these studies is to determine the mechanism(s) of action of the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (delta-9-THC) on those dopamine containing systems thought to be pivotally involved in the reinforcing and psychotomimetic properties of drugs of abuse. Specifically, the effects of acute and chronic administration of delta-9- THC, and the endogenous brain constituent anandamide, on midbrain dopamine neurons (A9 & A10) have been selected for study. In the proposed experiments we will use single neuron extracellular recordings to determine the effects of various cannabinoids (psychoactive and non-psychoactive) on the rate and patterns of action potential generation, and importantly the effects of prolonged exposure to delta-9-THC on these parameters. In addition, intracellular recording from neurons in the in vitro midbrain slice preparation will be used to analyze the effects of acute and chronic delta-9-THC administration on neuronal membrane properties and excitability. These projects should enable us to characterize the consequences of delta-9-THC exposure on midbrain dopamine neurophysiology. The data derived from these experiments will provide information relevant to delta-9-THC's pharmacological effects on those dopamine neurons implicated in the emotional, cognitive and sensorimotor changes occurring with marijuana use.