BRAIN & BEHAVIORAL ALTERATIONS AFTER METHAMPHETAMINE

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• 批准号: 7369349
• 负责人: William P. Melega
• 金额: $ 0.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369349
• 关键词: BRAIN; BEHAVIORAL; ALTERATIONS; AFTER; METHAMPHETAMINE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Behavioral consequences of human methamphetamine (METH) abuse have been extensively documented. However, underlying neurobiological mechanisms for those behaviors remain unspecified. A more precise and thorough examination of those processes still requires the use of appropriate animal models that address the broad range of abuse patterns in humans. For the proposed studies, we will model aspects of human chronic METH exposure in nonhuman primates with an integrated evaluation of biological, psychological, and environmental determinants. A 6 month escalating METH dose protocol that reflects human METH abuse patterns will be administered to vervet monkeys (Cercopithecus aethiops sabaeus) housed in naturally composed social groups. Presynaptic striatal dopamine (DA) transporter binding decreases will be determined in vivo throughout the study with PET to establish its sensitivity as an in vivo index of behavioral reactivity to METH. Behavioral alterations of impulsivity, aggression, and social relationships will be evaluated throughout the METH exposure and then continued for 6 months post-METH abstinence period to assess potential recovery. Cognitive alterations will be assessed by a battery of neuropsychological tasks. Individual differences in behavioral reactivity to METH, which are often seen in humans, will be evaluated in our METH subjects by measurement of pre-METH CSF monoamine metabolite levels (HVA, 5-HIAA, MHPG) and the extent of their changes, post-METH. Neurotoxicity of METH as expressed in dopamine and serotonin pathways within cortical, nigrostriatal and limbic regions will be evaluated by post-mortem measures of substantia nigra cell loss, pre-synaptic transporter and post-synaptic receptor densities (DA 1, DA2, 5-HT 1 A, 5-HT2A). The results will show in socially-housed adult nonhuman primates, the vulnerability of regional brain systems to METH exposure in conjunction with specific behavioral and cognitive assessments. This paradigm will represent a validated primate model to evaluate the efficacy of pharmacotherapies designed for treatment of neurological and behavioral deficits associated with human METH abus

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。人类滥用甲基苯丙胺(冰毒)的行为后果已被广泛记录在案。然而，这些行为的潜在神经生物学机制仍未明确。要对这些过程进行更精确和彻底的检查，仍然需要使用适当的动物模型来处理人类广泛的虐待模式。在拟议的研究中，我们将模拟人类在非人类灵长类动物中慢性冰毒暴露的各个方面，并对生物、心理和环境决定因素进行综合评估。一项反映人类冰毒滥用模式的6个月递增冰毒剂量协议将被实施给寄养在自然组成的社会群体中的马尾猴(CerCopithecus AethiopsSabaeus)。在整个PET研究中，将在体内测定突触前纹状体多巴胺(DA)转运体结合减少，以确定其敏感性作为体内行为对冰毒反应的指标。在整个冰毒暴露期间，将评估冲动、攻击性和社会关系的行为变化，然后在冰毒戒断后持续6个月，以评估潜在的康复。认知改变将通过一系列神经心理学任务进行评估。在我们的冰毒受试者中，对冰毒的行为反应性的个体差异将通过测量冰毒前脑脊液单胺代谢物水平(HVA、5-HIAA、MHPG)以及它们在冰毒后的变化程度来评估。通过死后测量黑质细胞丢失、突触前转运体和突触后受体密度(DA1、DA2、5-HT1A、5-HT2A)来评估皮质、黑质纹状体和边缘区多巴胺和5-羟色胺通路中甲基的神经毒性。结果将显示在社交寄居的成年非人类灵长类动物中，区域大脑系统对冰毒暴露的脆弱性，并结合特定的行为和认知评估。这一范例将代表一个经过验证的灵长类动物模型，以评估为治疗与人类冰毒相关的神经和行为缺陷而设计的药物疗法的有效性。