Clinical Trial of Dopamine-Serotonin Medication Combination in Cocaine Dependence

在过去的4年里，自从资助这个项目以来，UT Houston SAR-MDC已经表明可卡因 依赖与行为缺陷有关，包括决策，行为抑制， 更广泛的冲动性临床概念同样，我们发现可卡因依赖者之间的差异 和非药物使用对照对脑结构的磁共振成像（MRI）测量， 功能此外，我们获得的数据显示，在可卡因使用者中， 这些行为缺陷与大脑结构、大脑功能的改变以及治疗不当之间的联系 反应 对于这个项目的更新，重点将推进到确定这些大脑MRI的具体作用 通过精心选择的功能和结构MRI电池的治疗结果发现 技术，以预测治疗反应的特定类别的药物的基础上的机制， 行动上我们先前的血氧水平依赖（BOLD）fMRI数据显示，可卡因依赖 受试者（相对于对照组）（1）背外侧前额叶皮质、纹状体和丘脑激活较少 在工作记忆任务，可能反映受损的多巴胺功能;（2）更大的激活， 内侧眶额皮层在Go-Nogo任务的脉冲反应期间，可能反映受损 5-羟色胺功能;和（3）内侧眶额皮质和内侧额叶皮质的更大激活后， 反向学习任务的负反馈，也可能反映5-羟色胺功能受损。在 为了跟踪这些数据的治疗意义，本项目将研究（a）治疗前的大脑 作为神经递质特异性治疗反应的预测因子的这些任务的激活，和（B）早期 药物治疗三周后，任务相关的fMRI激活的变化作为后续治疗的预测因子。 长期神经递质特异性治疗反应。此外，治疗之间的关系 通过扩散张量MRI（DTI）测量的白质结构完整性的反应和测量， 将检查磁化传递率MRI（MTR）。

Over the last 4 years since the funding of this project, the UT Houston SAR-MDC has shown that cocaine dependence is associated with behavioral deficits including decision-making, behavioral inhibition, and the broader clinical construct of impulsivity. Likewise, we found differences between cocaine dependent subjects and non-drug using controls on Magnetic Resonance Imaging (MRI) measures of brain structure and function. In addition, we have acquired data showing that within cocaine users there is an association between these behavioral deficits and alterations in brain structure, brain function, and poor treatment response. For the renewal of this project, the focus will advance to determining the specific role of these brain MRI findings in treatment outcome by means of a carefully chosen battery of functional and structural MRI techniques in order to predict treatment response to specific classes of medication based on mechanism of action. Our previous blood oxygen level dependent (BOLD) fMRI data showed that cocaine dependent subjects (relative to controls) have (1) less dorsolateral prefrontal cortical, striatal, and thalamic activation during a working memory task, possibly reflecting impaired dopamine function; (2) greater activation in medial orbitofrontal cortex during impulsive responding on a Go-Nogo task, possibly reflecting impaired serotonin function; and (3) greater activation in medial orbitofrontal cortex and medial frontal cortex after negative feedback on a reversal learning task, also possibly reflecting impairment of serotonin function. In order to follow-up the treatment implications of this data, this project will examine (a) pretreatment brain activation on these tasks as predictors of neurotransmitter-specific treatment response, and (b) eariy changes (after three weeks of pharmacotherapy) in task-related fMRI activation as predictors of subsequent longer-term neurotransmitter-specific treatment response. In addition, the relationship between treatment response and measures of white-matter structural integrity as measured by diffusion tensor MRI (DTI) and magnetization transfer ratio MRI (MTR) will be examined.