The role of impulsivity in the development and maintenance of drug addiction

药物成瘾的特征是强迫服用药物和在限制药物摄入量方面失去控制。大多数研究人员都认为，强迫性药物使用的发展是因为大脑多巴胺系统对反复接触药物变得敏感。相比之下，人们对调节冲动或不受控制的吸毒的大脑变化知之甚少。我们的研究考察了冲动和药物成瘾之间的关系，使用这种疾病的既定动物模型。人类的冲动与血清素水平的降低和前额皮质的损伤有关。成瘾者在这两个系统中都表现出异常，这导致了一种假设，即长期滥用药物会产生神经变化，从而增加冲动，导致进一步吸毒。令人惊讶的是，我们之前的工作表明，长期接触可卡因对冲动的影响很小，尽管它确实改变了前额皮质中的血清素机制。我们现在提议调查这些影响是否在青春期更为明显，这个时期的特点是冲动，更容易上瘾，前额叶皮层发生了巨大的发育变化。我们还将研究上瘾和其他精神疾病（包括暴食症）中的冲动是否代表同样的现象。暴饮暴食症与药物成瘾相似，其特征是不受控制（即去抑制）摄入美味（即奖励）的食物。而且，就像毒瘾一样，目前还不清楚这种异常行为产生的原因。我们的工作可能会揭示增加这种行为的机制（生物和环境）。从长远来看，我们的研究可能有助于消除，甚至扭转，与药物成瘾相关的冲动行为的潜在悲剧性后果。此外，了解在吸毒和未吸毒状态下控制行为的偶然性可能最终导致治疗成瘾的新疗法的发展。

Drug addiction is characterised both by compulsion to take the drug and loss of control in limiting drug intake.  Most researchers agree that compulsive drug use develops because brain dopamine systems become sensitised with repeated drug exposure.  In contrast, little is known about the brain changes that mediate impulsive or uncontrolled drug-taking.  Our research examines the relationship between impulsivity and drug addiction, using established animal models of this disorder.  Impulsivity in humans is associated with reductions in serotonin levels and damage to the prefrontal cortex.  Addicts show abnormalities in both systems, leading to the hypothesis that chronic drug abuse produces neural changes that increase impulsivity and lead to further drug use.  Surprisingly, our previous work demonstrates that long-term exposure to cocaine produces minimal effects on impulsivity, although it does alter serotonin mechanisms in the prefrontal cortex.  We now propose to investigate whether these effects are more pronounced in adolescence, a period characterized by impulsivity, increased vulnerability to addiction and dramatic developmental changes in the prefrontal cortex.  We will also examine whether impulsivity in addiction and other psychiatric disorders, including binge eating disorder, represent the same phenomenon.  Binge eating disorder is similar to drug addiction in that it is characterized by uncontrolled (i.e., disinhibited) intake of highly palatable (i.e., rewarding) food.  And, like drug addiction, it is not clear why this aberrant behaviour develops.  Our work may shed light on the mechanisms (biological and environmental) that increase this behaviour.  In the long term, our research may help to eliminate, or even reverse, the potentially tragic consequences of impulsive behaviours associated with drug addiction.  Moreover, understanding the contingencies controlling behaviour in both drugged and undrugged states may ultimately lead to the development of novel therapies to treat addiction.