Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi
Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi
复制标题
DOI：
10.1016/j.ejphar.2006.08.034
复制
发表时间：
2006-11-21
影响因子：
5
通讯作者：
Kirstein, Cheryl L.
中科院分区：
文献类型：
--
作者：
Badanich, Kimberly A.;Adler, Kristopher J.;Kirstein, Cheryl L.
在人类中，青少年接触非法药物预示着成年人吸毒的开始，并表明早期吸毒会增加对吸毒成瘾的脆弱性。通过注射0、5或20 mg/kg可卡因并使其适应环境线索，测量了青春期早期[出生后（PND）35天]、青春期晚期（PND 45天）和年轻成年（PND 60天）大鼠的可卡因条件性位置偏好。在高剂量下，发现所有年龄段的人都有服用避孕药的偏好。PND 35是唯一偏好低剂量的年龄组。为了解决是否年龄相关的差异，可卡因的位置偏好与中脑边缘多巴胺能系统的差异，我们测量了细胞外多巴胺水平在隔隔核PND 35，PND 45和PND 60大鼠通过定量微透析在瞬态条件下。每天向大鼠注射5 mg/kg/ip或生理盐水，持续4天，并通过手术植入针对伏隔核的微透析探针。用0、1、10或40 nM多巴胺灌注大鼠，并测量细胞外多巴胺浓度。我们的研究结果表明，青少年的基础多巴胺与成人不同。所有可卡因治疗的大鼠，无论年龄大小，显示出响应于可卡因挑战的多巴胺超过基线的显著增加。此外，在提取分数（E-d）中存在年龄相关的差异，这是多巴胺再摄取的间接测量。这些研究结果表明细胞外多巴胺和多巴胺再摄取的个体发育差异，这些差异可能为青少年成瘾的脆弱性提供了解释。(c)2006 Elsevier B. V.保留所有权利。
In humans, adolescent exposure to illicit drugs predicts the onset of adult drug abuse and suggests that early drug use potentiates vulnerability to drug addiction. Cocaine conditioned place preferences were measured in early adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them to environmental cues. Cocaine preferences were found for all ages at the high dose. PND 35s were the only age group to have a preference at the low dose. To address whether age-related differences in cocaine place preferences were related to differences in the mesolimbic dopaminergic system, we measured extracellular dopamine levels in the nucleus accumbens septi of PND 35, PND 45 and PND 60 rats via quantitative microdialysis under transient conditions. Rats were injected daily with either 5 mg/kg/ip or saline for 4 days and surgically implanted with a microdialysis probe aimed at the nucleus accumbens. Rats were perfused with either 0, 1, 10 or 40 nM dopamine and the extracellular dopamine concentration was measured. Our results show that adolescents differ from adults in basal dopamine. All cocaine treated rats, regardless of age, showed a significant increase in dopamine over baseline in response to a cocaine challenge. Additionally, there were age-related differences in the extraction fraction (E-d), an indirect measure of dopamine reuptake. Together these findings suggest ontogenetic differences in extracellular dopamine and dopamine reuptake and that these differences may provide an explanation for adolescent vulnerability to addiction. (c) 2006 Elsevier B.V. All rights reserved.