Department of Experimental Medicine and Public Health, University of Camerino, Camerino, Italy.
Alcohol Clin Exp Res. 2010 Jan;34(1):90-7. doi: 10.1111/j.1530-0277.2009.01070.x. Epub 2009 Oct 23.
Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal.
Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB).
At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test.
Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant.
酒精中毒是一种慢性疾病，其特征是频繁醉酒，随后出现戒断发作和复饮。与这些醉酒和戒断周期相关的神经可塑性变化被认为在疾病进展中起关键作用。最近，已经表明，神经肽 S（NPS），一种新的孤儿肽受体系统，促进了实验室动物对酒精寻求的复发。鉴于酒精中毒的历史可能增加对酒精成瘾的易感性，我们试图确定 NPS 受体（NPSR）基因表达是否在戒断期间发生改变。
大鼠通过口服酒精给药进行 1 周的中毒。在最后一次酒精给药后 12 小时和 7 天，通过原位杂交分析大鼠 NPSR 基因表达。为了研究在长期戒断后 7 天 NPSR 系统适应的功能意义，我们使用电击探头防御性埋藏测试（DB）测试了 NPS 在非依赖和依赖后大鼠中的抗焦虑样特性。
在两个时间点，在包括内嗅核、运动皮层和内侧杏仁核在内的几个脑区观察到 NPSR 基因表达增加。在外侧下丘脑、室旁核、基底外侧和中央杏仁核也发现了中度增加的基因表达。与对照动物相比，在 7 天的禁欲后差异更为明显。通过功能数据证实了 NPSR 系统的上调，表明脑室内（ICV）NPS 给药（0.0、0.3 和 0.1 nmol/大鼠）在依赖后动物中引起更明显的抗焦虑作用，而不是在接受电击探头 DB 测试的对照动物中。
依赖后大鼠不同脑区的 NPSR mRNA 表达增加；如 DB 测试所示，这种表达变化具有功能相关性。
