TREATMENT OF ADDICTIONS-BIOLOGICAL CORRELATES

海洛因、可卡因和酒精成瘾，无论是单独的还是联合的，连同它们的多种和频繁的医学并发症（包括乙型肝炎和丙型肝炎、艾滋病和精神疾病），仍然是我们国家和世界大部分地区面临的主要医学问题。有效的治疗必须以对每一种特定成瘾疾病的生物学基础的基本了解为基础，包括长期接触特定滥用药物的影响以及与环境和遗传因素的相互作用。我们的NIH-NIDA P60治疗研究中心“成瘾治疗：生物学相关性”将继续识别和研究海洛因和可卡因引起的动态分子、神经生物学和行为变化。研究将集中于内源性阿片系统，阐明其在成瘾性疾病的生物学基础中的重要性，以及与相关神经递质和神经肽的相互作用，重点关注多巴胺能和谷氨酸能系统，以及应激反应系统。所有实验室和临床研究以及研究核心都是在互动的基础上开发的，并为整个中心提供专题整合。双向转化研究是本中心工作的一大特色。基础和应用临床研究的结果用于制定特定的假设和开发新的动物模型。实验室研究的结果（如抗利尿激素的改变）被应用于创新的临床研究。具体研究项目包括：1)研究海洛因或可卡因暴露、戒断和再暴露的影响，阿片系统中成瘾样行为变化的动态神经生物学适应；2)药物滥用对应激反应脑系统和下丘脑-垂体-肾上腺轴功能的影响；3)可卡因诱导的大脑边缘区突触可塑性；4)特定成瘾疾病中神经内分泌应激反应的改变，无或有相互依赖或共病。提高现有治疗方法的有效性和开发新的治疗方法取决于扩大我们对成瘾分子神经生物学的见解，这是这些项目的主要目标，每个项目利用五个核心资源，包括一个研究培训核心。专题整合和科学互动促进了协同作用，这只有一个多学科中心才能提供。

Heroin, cocaine, and alcohol addictions, alone and in combination, along with their multiple and frequent medical complications (including hepatitis B and C, AIDS, and psychiatric comorbidity) remain the major medical problems confronting our nation and much of the world. Effective treatments must be based on a fundamental understanding of the biological bases of each specific addictive disease, including the effects of chronic exposure to specific drugs of abuse and the interaction with environment and genetic factors. Our NIH-NIDA P60 Treatment Research Center, "Treatment of Addictions: Biological Correlates," will continue to identify and study the dynamic molecular, neurobiological, and behavioral changes caused by heroin and cocaine. Research will focus on the endogenous opioid system, to elucidate its importance in the biological basis of addictive diseases, and interactions with related neurotransmitters and neuropeptides, emphasis on dopaminergic and glutamatergic systems, and stress-responsive systems. All laboratory and clinical research studies, and the Research Cores, have been developed on an interactive basis with thematic integration for the entire Center. Bidirectional translational research is a hallmark of the work of this Center. Findings from basic and applied clinical research are used to formulate specific hypotheses and develop novel animal models. Findings from laboratory research (such as vasopressin alterations) are applied into innovative clinical research. The specific research projects include: 1) studies of the effect of exposure, withdrawal, and re-exposure to heroin or cocaine, dynamic neurobiological adaptations in the opioid system underlying addictive-like behavioral changes; 2) effects of drugs of abuse on stress-responsive brain systems and hypothalamic-pituitary-adrenal axis function; 3) cocaine-induced synaptic plasticity in limbic brain regions; and 4) alterations in neuroendocrine stress responsivity in specific addictive diseases without or with codependency or comorbidity. Increasing effectiveness of existing treatments and developing novel treatments depends on expanding our insights into the molecular neurobiology of addictions, which is the primary goal of these projects, each utilizing five core resources, including a Research Training Core. Thematic integration and scientific interaction fosters synergism, which only a multidisciplinary center can provide.