COCAINE ABUSE AND ALTERATIONS IN SEROTONERGIC FUNCTION

可卡因滥用和血清素功能的改变

• 批准号: 2122729
• 负责人: LAURE B BUYDENS-BRANCHEY
• 金额: $ 11.53万
• 依托单位: NARROWS INSTITUTE FOR BIOMEDICAL RES INC
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2122729
• 关键词: blood chemistry; cocaine; drug abuse chemotherapy; drug abuse therapy; drug addiction; drug interactions; drug withdrawal; fenfluramine; human subject; interview; medical records; neurochemistry; neuroendocrine system; neuropsychological tests; neurotransmitters; personality tests; physical chemical interaction; questionnaires; serotonin; serotonin inhibitor; statistics /biometry; substance abuse related disorder

Most of the information available at present about the biological underpinnings of cocaine effects derives from animal studies. These studies have shown that the dopaminergic system plays an important role in many of cocaine effects but that this role is not exclusive. Cocaine has a diversity of neurochemical actions involving the nonadrenergic and serotonergic systems as well as other neurotransmitter systems whose role still remains somewhat undetermined. The wealth of preclinical data on neurotransmitter alterations associated with cocaine administration is not matched by information derived from human studies. in man, much is known about the epidemiology of cocaine use, about its patterns of use and about the psychopathology associated with its consumption and discontinuation but our knowledge of neurochemical alterations underlying cocaine actions is still lagging. Information about neurochemical alterations preceding cocaine abuse is also extremely scarce. In order to gain information about the serotonergic function of individuals who engage in a lifestyle of cocaine abuse we studied their responsivity to challenges with a postsynaptic partial agonist, meta- chlorophenylpiperazine (mCPP) and compared it to the responsivity of healthy volunteers. Cocaine abusers differed significantly from control subjects. They displayed a psychological hyperresponsivity and a neuroendocrine hyporesponsivity to m-CPP. Associations were also found between personality characteristics indicating a poor impulse, mood and aggression control and psychological changes observed in response to m- CPP. These data could indicate that serotonin plays a role in the pathogenesis of cocaine addiction, at least in some individuals. The effects of cocaine itself could however not be assessed because our subjects were studied only once during the second week of an inpatient stay. The present proposal involves sequential assessments following cocaine discontinuation of the serotonergic function of individuals whose drug of choice has been cocaine for at least 3 years and who have used cocaine exclusively for a period of 6 months prior to the start of the study. The serotonergic function will be assessed through challenges with m-CPP and an indirect serotonin agonist, fenfluramine (FEN). Personality assessments will be done and psychological and neuroendocrine responses to m-CPP and FEN assessed first after admission to an inpatient rehabilitation unit and 4 days after cocaine discontinuation, and again prior to discharge, 3 weeks later. Patients will then be followed for a period of 6 months to see whether any of the assessments outlined above predicts clinical course and outcome. The study we propose to do will give us information about disturbances in a neurotransmitter system believed to play a significant role in cocaine actions, about the persistence of neurotransmitter alterations after a cocaine free period of 3 to 4 weeks, about the role played by premorbid characteristics in neurotransmitter function in cocaine addicts and about the predictive values of psychological and biological alterations on clinical course 6 months later. One can hypothesize that there is an interplay between predisposing neurochemical alterations and the superimposed effects of cocaine. Cocaine addicts could be biologically heterogeneous and treatment needs might be different in subgroups of patients with different psychopathological and biological profiles.

目前大部分关于生物的信息 可卡因效应的基础源自 动物研究。 这些研究表明，多巴胺能系统 在许多可卡因效应中发挥着重要作用，但这种作用是 不排他性。可卡因具有多种神经化学作用，包括 非肾上腺素能系统和血清素能系统以及其他 神经递质系统，其作用仍然尚未确定。 与神经递质改变相关的大量临床前数据 可卡因管理与来自的信息不匹配 人类研究。在人类中，人们对可卡因的流行病学了解很多 使用，关于其使用模式以及相关的精神病理学 随着它的消费和停产，但我们的知识 可卡因作用背后的神经化学变化仍然滞后。 有关可卡因滥用之前的神经化学变化的信息是 也极为稀缺。 为了获得有关血清素能功能的信息 我们研究了那些具有滥用可卡因生活方式的人 对突触后部分激动剂挑战的反应性，元- 氯苯基哌嗪 (mCPP) 并将其与 健康的志愿者。可卡因滥用者与对照组有显着差异 科目。 他们表现出心理过度反应和 m-CPP 神经内分泌反应低下。还发现了关联 表明不良冲动、情绪和情绪的人格特征之间 攻击控制和观察到的响应 m- 的心理变化 菲律宾人民党。这些数据可能表明血清素在 可卡因成瘾的发病机制，至少在某些个体中如此。这 然而，可卡因本身的影响无法评估，因为我们 受试者在住院的第二周仅进行一次研究 停留。 目前的提案涉及对可卡因进行连续评估 服用药物的个体血清素能功能的终止 选择可卡因至少 3 年并且使用过可卡因 仅限研究开始前 6 个月的时间。这 血清素能功能将通过 m-CPP 和 一种间接血清素激动剂芬氟拉明（FEN）。性格评估 将完成对 m-CPP 的心理和神经内分泌反应 进入住院康复病房后首先进行 FEN 评估， 停用可卡因后 4 天以及出​​院前再次进行 3 几周后。然后将对患者进行为期 6 个月的随访，以 看看上述评估是否可以预测临床病程 和结果。 我们建议进行的研究将为我们提供有关干扰的信息 据信在可卡因中发挥重要作用的神经递质系统 行动，关于神经递质改变后的持续性 戒除可卡因期3至4周，约起到病前作用 可卡因成瘾者神经递质功能的特征及其相关性 心理和生物改变的预测价值 6个月后的临床过程。 人们可以假设有一个 诱发神经化学改变和 可卡因的叠加效应。可卡因成瘾者可能是生物学上的 亚组中的异质性和治疗需求可能不同 具有不同心理病理学和生物学特征的患者。