A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice
A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice
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DOI：
10.1016/s0028-3908(99)00115-x
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Laviola, G
中科院分区：
文献类型：
--
作者：
Adriani, W;Laviola, G
确定易受药物滥用影响的关键个体发育期可能具有重要的心理生物学和临床治疗意义。下丘脑-垂体-肾上腺（HPA）轴对压力和精神兴奋剂的反应中潜在的年龄相关差异已在青春期动物模型中进行了测试。将两种性别的青春期（PND 33;43）和成年（PND>60）小鼠用d-苯丙胺（AMPH; 0、2或10 mg/kg i. p.）并立即面临轻微的心理压力体验，即置于新环境中。对激素和行为特征进行详细的时间过程分析，在试验期间的不同时间点（注射前，NT组;注射后15、30或120 min）处死动物以采集躯干血液。基础皮质酮（CORT）水平（NT组）始终高于青少年期比成人。总的来说，血液CORT水平显着增加，发现在两个年龄的小鼠暴露于被迫新奇。然而，也观察到了重要的年龄相关差异，注射生理盐水的青春期前儿童在120分钟测试结束时仍然表现出运动水平升高：会话，并且未能显示出超过基线的CORT释放的增加特征，这是成年人的典型特征。在AMPH 2给药后，青春期表现出比成人低得多的运动过度活跃，并且在整个过程中也没有表现出在成人中观察到的CORT释放的增加。当用高AMPH治疗时。10剂量时，在青少年期发现了明显的运动过度活跃，然而，其表现出低得多的典型的成年人的刻板舔和啃行为。目前的研究结果表明，一个独特的配置文件的综合行为和生理hyporesponsivity在小鼠在围青春期。后者也代表了一个非常有用的模型，用于研究人类青少年易受药物滥用影响的心理生物学风险因素问题。(C)2000爱思唯尔科技有限公司版权所有。
The identification of critical ontogenetic periods of increased vulnerability to the effects of drugs of abuse could have a great psychobiological and clinical-therapeutical importance. Potential age-related differences in the response of the hypothalamic-pituitary-adrenal (HPA) axis to both stress and psychostimulants has been tested here in an animal model of adolescence. Periadolescent (PND 33;43) and Adult (PND>60) mice of both sexes were injected with d-amphetamine (AMPH; 0, 2, or 10 mg/kg i.p.) and immediately faced with a mild psychological stress experience, i.e.placement in a novel enviroment. A detailed time-course analysis of both hormonal and behavioral profiles was performed, with animals being sacrificed for trunk-blood collection sit different time-points during the test (before the injection, NT group; 15, 30, or 120 min after the injection). Basal corticosterone (CORT) levels (NT group) were consistently higher in periadolescents than in adults. As a whole, a marked increment of blood CORT levels was found in mice of both ages exposed to forced novelty. However, important age-related differences were also observed, with Saline-injected periadolescents still exhibiting elevated levels of locomotion at the end of the 120-min test: session and failing to show the increasing profile of CORT release over the baseline that was typical of adults. Upon an AMPH 2 administration, periadolescents exhibited a much lower profile of locomotor hyperactivity than adults, and also failed to show an increase across the course of the session in CORT release, that was observed in adults. When treated with the high AMPH. 10 dose, a marked locomotor hyperactivity was found in periadolescents, which however showed much lower levels of the stereotyped licking and gnawing behavior, that was typical of adults. The present results suggest a unique profile of integrated behavioral and physiological hyporesponsivity in mice during periadolescence. The latter also represents a very useful model for the study of the issue of psychobiological risk factors involved in vulnerability to drugs of abuse in human adolescents. (C) 2000 Elsevier Science Ltd. All rights reserved.