NEUROTOXIC HALLUCINOGENS: EFFECTS ON LEARNING

兔角膜-第VI神经反射的巴甫洛夫条件反射 包括瞬膜的延伸， 可靠的测量全方位的联想学习和 记忆，并已被证明是一个很好的模型 行为和药理学检查系统 药物影响学习和记忆的机制。 特别是联想学习，已经被证明是 对致幻药物的作用高度敏感， 能够改变对刺激的感觉处理过程， 条件反射 因此吲哚致幻剂d-麦角酸 二乙基酰胺（LSD）和苯乙胺致幻剂2，5- 二甲氧基-4-甲基苯丙胺（DOM）产生的变化， 在产生可靠幻觉所需的剂量下学习， 人（分别为1和50 μ g/kg）。 最近，另外两名 戊乙胺致幻剂 (MDA)和3，4-亚甲二氧基甲基苯丙胺（MDMA） 已被证明能产生明显不可逆的 对血清素神经元的神经毒性 的基本目的 目前的研究有五个方面。 首先，详细描述剂量 MDA和MDMA需要改变的收购和保留 条件反射的行为机制 药物发挥作用的通道 第二，确定 是否由MDA产生的对5-羟色胺神经元的损伤， MDMA导致学习和记忆的长期缺陷。 将通过组织学方法评价神经毒性作用， 通过测量两到三周后的单胺含量 停止药物治疗和蛋白质的长期变化 二维凝胶法测定的脑组织含量 电泳 第三，我们将检查药物的能力， 作为5-羟色胺拮抗剂和再摄取阻断剂， MDA和MDMA的行为和神经毒性作用。 第四、 我们将确定动物是否承受MDA和MDMA 诱发的脑损伤可能会在随后的风险， 5-羟色胺、多巴胺和胆碱能功能受损， 可能发生在衰老过程中。 第五，也是最后一点，我们将执行 LSD、DOM、d-安非他明和d- 甲基苯丙胺来验证我们的行为和 神经毒性作用。 这些研究将提供所需的 越来越多的人滥用这些信息 致幻剂和长期后果， 虐待

Pavlovian conditioning of the rabbit's corneal-VIth nerve reflex involving extension of the nictitating membrane provides a reliable measure of the full range of associative learning and memory and has been demonstrated to be an excellent model system for examining the behavioral and pharmacological mechanisms by which drugs affect learning and memory. Associative learning, in particular, has been demonstrated to be highly sensitive to the actions of hallucinogenic drugs due to their ability to alter the sensory processing of the stimuli used during conditioning. Thus the indole hallucinogen d-lysergic acid diethylamide (LSD) and the phenethylamine hallucinogen 2,5- dimethoxy-4-methylamphetamine (DOM) produce changes in learning at doses required to produce reliable hallucinations in humans (1 and 50 Mu g/kg, respectively). Recently, two other penethylamine hallucinogens 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) have been demonstrated to produce apparently irreversible neurotoxicity to serotonin neurons. The basic purpose of the present studies is fivefold. First, to describe in detail the doses of MDA and MDMA required to alter the acquisition and retention of conditioned responses and identify the behavioral mechanisms through which the drugs exert their effects. Second, to determine whether the damage to serotonin neurons produced by MDA and MDMA results in a long-term deficit in learning and memory. Neurotoxic effects will be evaluated by histological methods and by measurement of monoamine content two to three weeks after cessation of drug treatment and by long-term changes in protein content of brain as measured by two-dimensional gel electrophoresis. Third, we will examine the ability of drugs such as serotonin antagonists and reuptake blockers to block the behavioral and neurotoxic effects of MDA and MDMA. Fourth, we will determine whether animals sustaining MDA and MDMA induced brain damage might be at risk with respect to subsequent impairment of serotonin, dopamine and cholinergic functions, as might occur during aging. Fifth, and last, we will carry out similar studies with LSD, DOM, d-amphetamine and d- methamphetamine to verify the specificity of our behavioral and neurotoxic effects. These studies should provide needed information on the growing population of humans that abuse these hallucinogenic agents and the long-term consequences of such abuse.