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COCAINE ABUSE & ALTERATIONS IN SEROTONERGIC FUNCTION

可卡因滥用

基本信息

批准号：
6033722
负责人：
LAURE B BUYDENS-BRANCHEY
金额：
$ 2.95万
依托单位：
NARROWS INSTITUTE FOR BIOMEDICAL RES INC
依托单位国家：
美国
项目类别：
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

项目摘要

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.

目前关于生物学的大部分信息可卡因效应的基础来自于动物研究。这些研究表明多巴胺能系统在可卡因的许多作用中起着重要作用，不是排他性的。皮质醇具有多种神经化学作用，非肾上腺素能和肾上腺素能系统以及其他神经递质系统，其作用仍然有些不确定。关于神经递质改变的丰富临床前数据与可卡因管理的信息不匹配，人类研究在人类中，可卡因的流行病学使用，关于其使用模式以及相关的精神病理学它的消费和中断，但我们的知识，可卡因作用背后的神经化学变化仍然滞后。关于可卡因滥用前神经化学改变的信息是也极其稀缺。为了获得关于细胞的负能功能的信息，我们研究了那些有可卡因滥用生活方式的人，对突触后部分激动剂的反应性，氯苯基哌嗪（mCPP），并将其与健康志愿者可卡因滥用者与对照组有显著差异科目他们表现出心理上的过度反应，对m-CPP的神经内分泌低反应性。还发现了关联性格特征表明一个穷人的冲动，情绪和攻击控制和心理变化，观察到的反应，m- CPP。这些数据可能表明，血清素发挥作用，在可卡因成瘾的发病机制，至少在一些人。的然而，可卡因本身的影响无法评估，因为我们受试者仅在住院的第二周进行一次研究留下吧本提案涉及在可卡因之后进行的连续评估，药物治疗的个体的肾上腺素能功能的中止选择可卡因至少3年，并使用可卡因在研究开始前仅持续6个月的时间。的将通过用m-CPP激发来评估多巴胺能功能，一种间接血清素激动剂芬氟拉明（FEN）。个性评估将完成和心理和神经内分泌反应的m-CPP和入院后首次评估FEN，可卡因停药后4天，出院前再次，3 周后然后将对患者进行为期6个月的随访，查看上述评估是否可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一种被认为在可卡因中起重要作用的神经递质系统行动，关于持续的神经递质改变后，可卡因戒断期3 ~ 4周，约为病前所起的作用可卡因成瘾者神经递质功能的特点心理和生物学改变对临床病程6个月后。我们可以假设诱发性神经化学变化与可卡因的副作用可卡因成瘾者在生物学上异质性和治疗需求可能不同的亚组有着不同精神病理学和生理学特征的病人