Kabbaj M, Isgor C
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee 4300, FL 32306, USA.
Neurosci Lett. 2007 Jul 5;422(1):7-12. doi: 10.1016/j.neulet.2007.04.088. Epub 2007 Jun 9.
Previously, we have shown that chronic exposure to environmental and social stimuli (ESS) during adolescence prevents the development of behavioral sensitization to amphetamine in adult rats. At the onset of the peripubertal-juvenile period (28-d) male rats were subjected to a 28-d long intermittent ESS protocol or handled as controls (NO-ESS). Twenty-four hours after the last session of ESS or NO-ESS, all rats started a regimen of behavioral sensitization to amphetamine (1mg/kg, i.p.), in which rats were injected every third day with amphetamine or saline on four occasions. Then following one week abstinence all rats were challenged with a lower dose of amphetamine (0.5mg/kg, i.p.) and their locomotor activity monitored for 2h. Our results showed that while NO-ESS rats developed behavioral sensitization to amphetamine, ESS rats did not develop this behavior. All rats were then sacrificed 3 days following the challenge to allow for amphetamine clearance. Since mesolimbic dopamine has been implicated in behavioral sensitization to amphetamine we compared messenger RNA (mRNA) expression of key dopamine-related molecules in the mesolimbic circuitry in ESS and NO-ESS rats. A decrease in dopaminergic D1 receptor (D1R) gene expression in the caudate-putamen (CPu) was associated with amphetamine sensitization in the controls, possibly as a result of a chronic increase in DA release. In contrast, amphetamine treatment did not modulate D1R mRNA levels in ESS rats. No change has been detected in any other dopaminergic markers [D2R, D3R, tyrosine hydroxylase (TH) or dopamine transporter (DAT) mRNAs]. Consequently, we conclude that ESS may inhibit the development of behavioral sensitization to amphetamine through preventing the decrease in CPu D1R mRNA levels.
此前，我们已经表明，青春期长期暴露于环境和社会刺激（ESS）会阻止成年大鼠对苯丙胺产生行为敏化。在青春期前-幼年时期开始时（28日龄），雄性大鼠接受为期28天的间歇性ESS方案处理或作为对照进行处理（无ESS）。在ESS或无ESS的最后一次处理后24小时，所有大鼠开始对苯丙胺（1mg/kg，腹腔注射）进行行为敏化方案，在此方案中，大鼠每隔三天注射一次苯丙胺或生理盐水，共注射四次。然后，在禁欲一周后，所有大鼠接受较低剂量的苯丙胺（0.5mg/kg，腹腔注射）刺激，并监测其运动活动2小时。我们的结果表明，无ESS大鼠对苯丙胺产生了行为敏化，而ESS大鼠未出现这种行为。在刺激后3天，所有大鼠被处死，以便清除苯丙胺。由于中脑边缘多巴胺与对苯丙胺的行为敏化有关，我们比较了ESS和无ESS大鼠中脑边缘回路中关键多巴胺相关分子的信使核糖核酸（mRNA）表达。在对照组中，尾状核-壳核（CPu）中多巴胺能D1受体（D1R）基因表达的降低与苯丙胺敏化有关，这可能是多巴胺（DA）释放长期增加的结果。相比之下，苯丙胺处理并未调节ESS大鼠中D1R mRNA水平。在任何其他多巴胺能标记物[D2R、D3R、酪氨酸羟化酶（TH）或多巴胺转运体（DAT）mRNA]中均未检测到变化。因此，我们得出结论，ESS可能通过阻止CPu中D1R mRNA水平的降低来抑制对苯丙胺的行为敏化的发展。
