Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models
Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models
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DOI：
10.1016/s0149-7634(99)00032-9
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发表时间：
1999-11-01
影响因子：
8.2
通讯作者：
Gerra, G
中科院分区：
文献类型：
--
作者：
Laviola, G;Adriani, W;Gerra, G
青春期与发生药物滥用/依赖的风险增加有关。在个体发育阶段，大脑和荷尔蒙系统仍在经历关键的成熟重新安排，这与心理社会发展的重大变化一起发生。然而，青春期的神经激素和行为方面与MDMA(摇头丸)和安非他明(安非他明)等精神刺激剂的脆弱性有关的研究很少。追求新奇是这个年龄段的典型气质/行为特征，可能会在很大程度上导致心理和心理生物上的脆弱性。在人类中，与对照组相比，新奇感觉寻求得分升高和单胺功能紊乱都与青春期晚期服用MDMA的人相关。在青春期前的动物模型中，寻找新的刺激和感觉实际上与精神刺激剂共享一个共同的神经生物学底物(与奖励相关的大脑中脑边缘通路)。本综述总结了最近在老鼠身上所做的工作，这些工作表明，青春期前的受试者的特征是不平衡和“极端导向”的行为，与成年人相比，他们对新奇事物的追求更高。反复和间歇地服用可卡因或安非他明与青春期前明显的运动敏感化有关，这种敏感化没有表现出成年人典型的刻板行为综合症的明显敏感化--可能与福利不良有关。在青春期期间，还发现了一种独特的综合行为和生理低反应性，对强迫新奇和急性AMPH注射都是如此。总体而言，这些结果以及之前在这一主题上的研究表明，与年龄较大的动物相比，青春期前的动物可能更容易受到AMPH相关厌恶属性的保护，也可能更容易受到内在奖赏状态的影响。因此，目前的青春期动物模型似乎是一种可靠和有用的方法，可以用来研究对各种习惯形成因素或情感体验的易感性，这些因素的积极强化特性可能依赖于共同的神经生物学底物。深入了解青春期心理刺激对遗传、神经生物、心理社会和环境因素之间复杂相互作用的影响，将有助于更早、更有效地预防和治疗。(C)1999爱思唯尔科学有限公司。保留所有权利。
Adolescence is associated with an increased risk of developing drug abuse/dependence. During this ontogenetic phase, brain and hormonal systems are still undergoing crucial maturational rearrangements, which take place together with significant modifications in psychosocial development. However, the neurohormonal and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants such as MDMA ("Ecstasy") and amphetamine (AMPH). Novelty-seeking, a temperamental/behavioral trait that is typical of this age period, might substantially contribute to both psychological and psychobiological vulnerability. In humans, an elevated score of novelty-sensation seeking and a derangement of monoaminergic function were both associated with late adolescence MDMA users compared to controls. In animal models of periadolescence, the search for novel stimuli and sensations actually shares a common neurobiological substrate (the reward-related brain mesolimbic pathways) with psychostimulants. The present review summarises recent work in mice, which indicates that periadolescent subjects are characterized by an unbalanced and "extremes-oriented" behavior and by elevated novelty-seeking compared to adults. Repeated and intermittent administration of cocaine or AMPH was associated with the development of a prominent locomotor sensitization in periadolescents, which failed to exhibit the marked sensitization of the stereotyped behavioral syndrome-possibly associated with poor welfare-that was typical of adults. A unique profile of integrated behavioral and physiological hyporesponsivity to both forced novelty and acute AMPH administration during periadolescence was also found. As a whole, these results, together with previous work on this topic, suggest that periadolescents may be more "protected" from AMPH-related aversive properties, and perhaps more vulnerable to the experience of internal states of reward, than older animals. Thus, the present animal model of adolescence seems to represent a reliable and useful method for the investigation of vulnerability to a variety of habit-forming agents or emotional experiences whose positive reinforcing properties may rely on common neurobiological substrates. A deeper understanding of psychostimulant effects during adolescence on the complex interaction between genetic, neurobiologic, psychosocial, and environmental factors will lead to earlier and more effective prevention and treatment. (C) 1999 Elsevier Science Ltd. All rights reserved.