Everitt Barry J, Belin David, Economidou Daina, Pelloux Yann, Dalley Jeffrey W, Robbins Trevor W
Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge, UK.
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3125-35. doi: 10.1098/rstb.2008.0089.
We hypothesize that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntary drug use through the loss of control over this behaviour, such that it becomes habitual and ultimately compulsive. We describe evidence that the switch from controlled to compulsive drug seeking represents a transition at the neural level from prefrontal cortical to striatal control over drug-seeking and drug-taking behaviours as well as a progression from ventral to more dorsal domains of the striatum, mediated by its serially interconnecting dopaminergic circuitry. These neural transitions depend upon the neuroplasticity induced by chronic self-administration of drugs in both cortical and striatal structures, including long-lasting changes that are the consequence of toxic drug effects. We further summarize evidence showing that impulsivity, a spontaneously occurring behavioural tendency in outbred rats that is associated with low dopamine D2/3 receptors in the nucleus accumbens, predicts both the propensity to escalate cocaine intake and the switch to compulsive drug seeking and addiction.
我们假设药物成瘾可被视为一系列转变的终点，这些转变始于最初的自愿使用药物，随后失去对该行为的控制，使其变得习以为常并最终成瘾。我们阐述了相关证据，即从受控制的药物寻求转变为强迫性药物寻求，代表着在神经层面上，从额叶前皮质对药物寻求和用药行为的控制转变为纹状体的控制，同时也是纹状体从腹侧到背侧区域的进展，这一过程由其串联的多巴胺能神经回路介导。这些神经转变依赖于长期自我给药在皮质和纹状体结构中诱导的神经可塑性，包括因药物毒性作用而产生的持久变化。我们进一步总结了证据，表明冲动性是远交系大鼠中一种自发出现的行为倾向，与伏隔核中低水平的多巴胺D2/3受体相关，它既能预测可卡因摄入量增加的倾向，也能预测向强迫性药物寻求和成瘾的转变。
