BRAIN STRUCTURE AND FUNCTION AFTER DRUGS OF ABUSE

滥用药物后的大脑结构和功能

• 批准号: 3211887
• 负责人: Robert S Sloviter
• 金额: $ 12.06万
• 依托单位: NEW YORK STATE DEPARTMENT OF HEALTH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211887
• 关键词: brain cell; chronic brain damage; cognition disorders; dosage; drug abuse; drug adverse effect; electron microscopy; electrophysiology; gamma aminobutyrate; hallucinations; hippocampus; histochemistry /cytochemistry; immunochemistry; immunocytochemistry; laboratory rat; microscopy; neural degeneration; neuroanatomy; neurologic manifestations; neuropeptides; neurophysiology; psychotomimetic drug; psychotropic drugs; reflex epilepsy; silver impregnation; social behavior disorders

Two hypotheses are described. The first predicts that psychotomimetic and hallucinogenic drugs that cause similar behaviors in humans may share a common locus of action in the limbic system. The second hypothesis states that some drugs of abuse may cause long-lasting behavioral, mood and cognitive deficits as a result of irreversible brain damage. The first hypothesis derives from several related observations. First is the fact that a number of compounds, many related structurally to amine neurotransmitters, induce behaviors in humans that are difficult to distinguish from some spontaneous psychotic behaviors. The second observation is that in idiopathic temporal lobe epilepsy, a neurological disorder characterized in part by abnormal hippocampal neurotransmission, non-psychotic patients often exhibit behaviors characteristic of psychosis and that these behaviors occur when hippocampal discharges arise. The first hypothesis to be tested is that the three parts of the triad described above, ie, psychotomimetic drugs, endogenous psychosis and psychotic manifestations of temporal lobe epilepsy, may share a common underlying locus. Specifically, abnormal hippocampal activity may cause behaviors common to all three hallucinatory states regardless of the molecular mechanism(s) involved. This hypothesis will be tested by determining the effects of drugs of abuse on hippocampal responses, excitability and inhibition in vivo using electrophysiological methods. The second hypothesis to be tested is that some drugs of abuse produce persistent behavioral deficits as the results of irreversible brain damage. Given recent advances on the subject of irreversible cell death and the mechanisms that cause it, it is important to determine if drugs of abuse cause irreversible damage, which drugs do so under what conditions and whether or not this cell damage can be prevented. This will be done using neuroanatomical methods, including silver stain for neuronal degeneration, immunocytochemistry of GABA-, amine- and peptide-positive neurons, as well as electron microscopy. The biomedical impact of preventing drug-induced brain damage, if it occurs, would be considerable.

描述了两个假设。 第一个预测， 精神病和致幻药物，导致类似 人类的行为可能有一个共同的行动轨迹， 边缘系统 第二个假设指出，一些药物， 虐待可能会导致长期的行为，情绪和认知 由于不可逆的脑损伤而导致的缺陷。 第一个假设来自几个相关的观察。 首先是一些化合物， 在结构上与胺神经递质结合， 很难区分人类和一些自发的 精神病行为 第二个观察结果是， 颞叶癫痫是一种神经系统疾病， 海马神经传递异常，非精神病性 患者通常表现出精神病的行为特征， 这些行为发生在海马放电出现时。 第一个要检验的假设是， 上述三联征，即拟精神病药物，内源性 颞叶癫痫的精神病和精神病表现， 可能有共同的潜在基因座 具体来说，异常 海马体的活动可能会导致这三种行为的共同点 无论分子机制如何的幻觉状态 涉案 这一假设将通过确定 滥用药物对海马反应，兴奋性的影响 和使用电生理学方法的体内抑制。 第二个有待检验的假设是， 由于以下原因而产生持续的行为缺陷 不可逆转的脑损伤 鉴于最近在这方面的进展 不可逆转的细胞死亡和导致它的机制，它是 必须确定滥用药物是否造成不可逆转 损害，哪些药物在什么条件下这样做，是否或 这种细胞损伤是无法避免的。 这将使用 神经解剖学方法，包括神经元的银染色 变性，GABA-，胺-和 肽阳性神经元，以及电子显微镜。 的 预防药物引起的脑损伤的生物医学影响，如果它 发生，将是相当大的。