CANNABINOIDS IN DOPAMINE NEURON ELECTROPHYSIOLOGY

大约有1000万人每月或更长时间使用大麻 频繁的基础上，使其成为最常用的非法药物。 2%第12 分级员每天都吸食大麻 此外，大麻的使用甚至 1992年，较低年龄（八年级）的学生增加了整整一个百分点。 健康人2000指大麻的使用是典型的年龄在第一次- 15岁以前使用与滥用程度较大有关的使用现象 和其他药物的作用。 这些事实再加上 具有精神活性的大麻素会产生无数的行为效应， 中枢神经系统内信息处理的改变， 内源性大麻素受体需要大量的努力， 了解其对中枢神经系统功能的影响。 的 这些研究的总体目标是确定 精神活性大麻素，δ-9-四氢大麻酚（δ-9-THC）， 这些含有多巴胺的系统被认为是中枢参与了 滥用药物的强化和拟精神病性质。 具体地，急性和慢性施用δ-9- 四氢大麻酚和内源性脑成分花生四烯酸对中脑多巴胺 选择神经元（A9和A10）用于研究。 拟议 我们将使用单个神经元细胞外记录来确定 各种大麻素（精神活性和非精神活性）对 动作电位产生的速率和模式，重要的是 长期暴露于δ-9-THC对这些参数的影响。 在 此外，来自体外中脑中神经元的细胞内记录 切片制备将用于分析急性和慢性 δ-9-THC给药对神经元膜性质的影响， 兴奋性 这些项目应该使我们能够描述 δ-9-THC暴露对中脑多巴胺神经生理学的影响。 从这些实验中获得的数据将提供有关信息 δ-9-THC对多巴胺神经元的药理作用 与情绪、认知和感觉运动的变化有关 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.