Acetyl-L-carnitine reduces impulsive behaviour in adolescent rats
Acetyl-L-carnitine reduces impulsive behaviour in adolescent rats
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DOI：
10.1007/s00213-004-1892-9
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Laviola, G
中科院分区：
文献类型：
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作者：
Adriani, W;Rea, M;Laviola, G
注意力缺陷/多动障碍（ADHD）可以影响人类婴儿和青少年。这种疾病的一个重要特征是行为冲动。本研究评估了慢性乙酰-L-肉毒碱（ALC，盐水或100 mg/kg SC，加上50 mg/kg口服）在经验证的ADHD动物模型中降低冲动性的能力。在青春期（出生后30-45天），食物限制的大鼠在带有两个鼻子戳孔的操作室中进行测试，一个立即递送一个食物颗粒，另一个延迟递送五个颗粒。延迟时间随天数增加（从0到80秒）。偏好-延迟曲线的个体差异出现了，并确定了两个不同的亚群，即一个具有接近水平的曲线，另一个具有非常陡峭的（“脉冲”）斜率。慢性ALC给药可轻微但持续降低冲动性。哌甲酯（MPH、生理盐水或3 mg/kg IP，每日两次）也获得了一致的结果。冲动大鼠表现出较低的代谢物/5-羟色胺（5 HIAA/5 HT）的比例在内侧额叶皮质（MFC）和较低的去甲肾上腺素（NA）水平在MFC和扣带回皮质（CC）相比，其他亚组。ALC处理增加了CC中的NA水平以及CC和MFC两者中的5 HIAA/5 HT比率。目前的数据表明，ALC，一种缺乏精神兴奋剂特性的药物，可能对ADHD儿童的治疗有一些有益的影响。
The attention deficit/hyperactivity disorder (ADHD) can affect human infants and adolescents. One important feature of this disorder is behavioural impulsivity. This study assessed the ability of chronic acetyl-L-carnitine (ALC, saline or 100 mg/kg SC, plus 50 mg/kg orally) to reduce impulsivity in a validated animal model for ADHD. Food-restricted rats were tested during adolescence (postnatal days, pnd, 30-45) in operant chambers with two nose-poking holes, one delivering one food pellet immediately, and the other five pellets after a delay. Delay length was increased over days (from 0 to 80 s). Individual differences in the preference-delay curve emerged, with the identification of two distinct subpopulations, i.e. one with a nearly horizontal curve and another with a very steep ("impulsive") slope. The impulsivity profile was slightly but consistently reduced by chronic ALC administration. Consistent results were also obtained with methylphenidate (MPH, saline or 3 mg/kg IP twice daily). Impulsive rats exhibited a lower metabolite/serotonin (5HIAA/5HT) ratio in the medial frontal cortex (MFC) and lower noradrenaline (NA) levels in the MFC and cingulate cortex (CC) when compared with the other subgroup. The ALC treatment increased NA levels in the CC and the 5HIAA/5HT ratio in both CC and MFC. Present data suggest that ALC, a drug devoid of psychostimulant properties, may have some beneficial effects in the treatment of ADHD children.