Effects of psychotropic drugs on second messenger signaling and preference for nicotine in juvenile male mice.
Effects of psychotropic drugs on second messenger signaling and preference for nicotine in juvenile male mice.
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DOI：
10.1007/s00213-014-3434-4
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发表时间：
2014-04
影响因子：
3.4
通讯作者：
Bolaños-Guzmán CA
中科院分区：
文献类型：
--
作者：
Alcantara LF;Warren BL;Parise EM;Iñiguez SD;Bolaños-Guzmán CA
儿童注意力缺陷/多动障碍（ADHD）和重度抑郁症（MDD）的常见治疗策略是哌醋甲酯（MPH）和氟西汀（FLX）联合治疗。这引起了人们的担忧，因为MPH+FLX治疗可能具有与可卡因类似的药效学特性，可能会增加药物滥用的可能性。检查溶剂、MPH、FLX、MPH+FLX和可卡因重复给药对幼龄（出生后[PD] 20-34天）和成年（PD 70-84天）雄性小鼠基因表达的短期和长期影响。我们进一步评估了青少年药物治疗是否会影响成年后对尼古丁的敏感性。幼年和成年C57 BL/6 J小鼠接受媒介物、MPH、FLX、MPH+FLX或可卡因，每天两次，连续15天。在最后一次药物注射后24小时或2个月处死小鼠，以评估药物对腹侧被盖区内细胞外信号调节蛋白激酶-1/2（ERK）通路的诱导作用。随后的敏感性尼古丁（0.05，0.07和0.09 mg/kg）使用位置调节范例（CPP）24小时和2个月后，青少年药物暴露。MPH+FLX或可卡因暴露于幼年小鼠中增加了ERK 2及其下游靶点（CREB，cFos和Zif 268）的mRNA表达，并增加了药物暴露后2个月ERK 2和CREB的蛋白磷酸化。在成年处理的小鼠中观察到类似的mRNA发现。药物治疗后24小时的基因表达结果是可变的。青少年药物暴露增加尼古丁的偏好时，在成年期进行测试。早期MPH+FLX或可卡因暴露同样会破坏ERK通路，这是一种与动机和情绪调节有关的信号级联，并增加成年后对尼古丁的敏感性。
A common treatment strategy for pediatric attention deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) is combined methylphenidate (MPH) and fluoxetine (FLX). This has raised concerns because MPH+FLX treatment may have pharmacodynamic properties similar to cocaine, potentially increasing drug abuse liability. To examine the short- and long-term consequences of repeated vehicle, MPH, FLX, MPH+FLX, and cocaine treatment on gene expression in juvenile (postnatal days [PD] 20–34) and adult (PD 70–84) male mice. We further assessed whether juvenile drug treatment influenced subsequent sensitivity for nicotine in adulthood. Juvenile and adult C57BL/6J mice received vehicle, MPH, FLX, MPH+FLX, or cocaine twice-daily for 15 consecutive days. Mice were sacrificed 24 h or 2 months after the last drug injection to assess drug-induced effects on the extracellular signal-regulated protein kinase-1/2 (ERK) pathway within the ventral tegmental area. Subsequent sensitivity for nicotine (0.05, 0.07, and 0.09 mg/kg) was measured using the place-conditioning paradigm (CPP) 24 h and 2 months after juvenile drug exposure. MPH+FLX, or cocaine exposure in juvenile mice increased mRNA expression of ERK2 and its downstream targets (CREB, cFos, and Zif268), and increased protein phosphorylation of ERK2 and CREB 2 months after drug exposure. Similar mRNA findings were observed in the adult-treated mice. Findings on gene expression 24 h following drug treatment were variable. Juvenile drug exposure increased preference for nicotine when tested in adulthood. Early-life MPH+FLX, or cocaine exposure similarly disrupts the ERK pathway, a signaling cascade implicated in motivation and mood regulation, and increases sensitivity for nicotine in adulthood.
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神经元型特异性信号，用于腹侧对段区域的奖励和惩罚。
影响因子：
64.8
作者：
Cohen, Jeremiah Y.;Haesler, Sebastian;Vong, Linh;Lowell, Bradford B.;Uchida, Naoshige
通讯作者：
Uchida, Naoshige
影响因子：
5
作者：
Bolanos, CA;Garmsen, GM;McDougall, SA
通讯作者：
McDougall, SA
影响因子：
7.6
作者：
Adriani, W;Macrì, S;Laviola, G
通讯作者：
Laviola, G
DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
Barrot, M;Olivier, JDA;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
2.3
作者：
Bolaños, CA;Neve, RL;Nestler, EJ
通讯作者：
Nestler, EJ