Laviola G, Pascucci T, Pieretti S
Section of Behavioural Pathophysiology, Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, viale Regina Elena 299, I-00161, Rome, Italy.
Pharmacol Biochem Behav. 2001 Jan;68(1):115-24. doi: 10.1016/s0091-3057(00)00430-5.
The neurobiological and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants. Periadolescent (33-43 days) and adult (>70 days) Sprague-Dawley rats underwent a 3-day treatment history with D-amphetamine (AMPH) at 0, 2, or 10 mg/kg (once a day). After a short 5-day-long withdrawal interval, freely moving animals were challenged with a 2-mg/kg AMPH dose and their behavior as well as in vivo intrastriatum dopamine (DA) release in the CNS were assessed. Microdialysis data indicated that AMPH-history periadolescent rats showed a prominent sensitization of AMPH-stimulated DA release, whereas no such change was found in adult subjects. As expected, acute AMPH administration strongly reduced time spent lying still and increased levels of cage exploration in animals of both ages. A treatment history of high AMPH dosage was associated with a marked sensitization of the exploratory behavior in adults, whereas it induced a quite opposite profile in periadolescents. The latter group only was also characterized by a compulsive involvement in the stereotyped head-bobbing response. These results indicate that differently from adults, marked alterations in neurobiological target mechanisms are observed in rats around periadolescence as a consequence of a quite mild regimen of intermittent AMPH exposure. Thus, a neurobiological substrate for an age-related increased vulnerability towards the addictive risks of these drugs is suggested.
与对精神兴奋剂的易感性相关的青少年神经生物学和行为方面的研究一直很少。对青春期前后（33 - 43天）和成年（>70天）的Sprague-Dawley大鼠进行为期3天的D-苯丙胺（AMPH）治疗，剂量为0、2或10mg/kg（每天一次）。经过短暂的5天停药期后，对自由活动的动物给予2mg/kg的AMPH剂量进行激发试验，并评估它们的行为以及中枢神经系统内纹状体内多巴胺（DA）的释放情况。微透析数据表明，有AMPH给药史的青春期前后大鼠对AMPH刺激的DA释放表现出显著的敏感性增强，而成年大鼠未发现此类变化。正如预期的那样，急性给予AMPH会显著减少两个年龄段动物静止不动的时间，并增加其在笼内探索的水平。高剂量AMPH的治疗史与成年动物探索行为的显著敏感性增强有关，而在青春期前后的大鼠中却产生了相反的情况。后一组大鼠还表现出对刻板的点头反应的强迫性参与。这些结果表明，与成年大鼠不同，青春期前后的大鼠由于相当温和的间歇性AMPH暴露方案，其神经生物学靶机制会出现明显改变。因此，提示存在一种与年龄相关的、对这些药物成瘾风险易感性增加的神经生物学基础。
