Nicolas Céline, Tauber Clovis, Lepelletier François-Xavier, Chalon Sylvie, Belujon Pauline, Galineau Laurent, Solinas Marcello
INSERM, U1084, Poitiers, France.
Université de Poitiers, U1084, Poitiers, France.
Neuropsychopharmacology. 2017 Sep;42(10):1981-1990. doi: 10.1038/npp.2017.109. Epub 2017 May 29.
The chronic and relapsing nature of addiction suggests that drugs produce persistent adaptations in the brain that make individuals with drug addiction particularly sensitive to drug-related cues and stress and incapable of controlling drug-seeking and drug-taking behavior. In animal models, several long-lasting neuroadaptations have been described. However, few studies have used brain-imaging techniques to provide a complete picture of brain functioning in the course of withdrawal from cocaine. In this study, we allowed rats to self-administer cocaine under short-access (1-h/day) or long-access (6-h/day) conditions and used 2-deoxy-2-(F)fluoro-d-glucose (FDG) positron emission tomography scanning to investigate the longitudinal changes in metabolic activity 1 and 4 weeks after discontinuation of cocaine self-administration. We found that compared to naive rats, both long-access and short-access rats showed significant disruptions in basal brain metabolic activity. However, compared to short-access, long-access rats showed more intense, and long-lasting neuroadaptations in a network of brain areas. In particular, abstinence from extended access to cocaine was associated with decreased metabolic activity in the anterior cingulate cortex, the insular cortex, and the dorsolateral striatum, and increased metabolic activity in the mesencephalon, amygdala, and hippocampus. This pattern is strikingly similar to that described in humans that has led to the proposal of the Impaired Response Inhibition and Salience Attribution model of addiction. These results demonstrate that extended access to cocaine leads to persistent neuroadaptations in brain regions involved in motivation, salience attribution, memory, stress, and inhibitory control that may underlie increased risks of relapse.
成瘾的慢性和复发性表明，药物会在大脑中产生持久的适应性变化，使成瘾个体对与药物相关的线索和压力特别敏感，且无法控制觅药和用药行为。在动物模型中，已经描述了几种持久的神经适应性变化。然而，很少有研究使用脑成像技术来全面了解可卡因戒断过程中的大脑功能。在本研究中，我们让大鼠在短时间给药（每天1小时）或长时间给药（每天6小时）条件下自行服用可卡因，并使用2-脱氧-2-（F）氟-D-葡萄糖（FDG）正电子发射断层扫描来研究可卡因自行给药停止后1周和4周代谢活动的纵向变化。我们发现，与未接触过可卡因的大鼠相比，长时间给药和短时间给药的大鼠在基础脑代谢活动方面均出现了显著紊乱。然而，与短时间给药的大鼠相比，长时间给药的大鼠在一组脑区中表现出更强烈、更持久的神经适应性变化。特别是，长时间接触可卡因后戒断与前扣带回皮质、岛叶皮质和背外侧纹状体的代谢活动降低以及中脑、杏仁核和海马体的代谢活动增加有关。这种模式与在人类中描述的模式惊人地相似，后者导致了成瘾的反应抑制和显著性归因受损模型的提出。这些结果表明，长时间接触可卡因会导致参与动机、显著性归因、记忆、压力和抑制控制的脑区出现持久的神经适应性变化，这可能是复发风险增加的基础。
