Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currently unclear if NAT-based mechanisms also play a role in drug-induced neuroadaptations. Aberrant regulation of gene expression is one critical factor underlying the long-lasting behavioral abnormalities that characterize substance use disorder, and it is possible that some drug-induced transcriptional responses are mediated, in part, by perturbations in NAT activity. To test this hypothesis, we used an automated algorithm that mines the NCBI AceView transcriptomics database to identify NAT overlapping genes linked to addiction. We found that 22% of the genes examined contain NATs and that expression of Homer1 natural antisense transcript (Homer1-AS) was altered in the nucleus accumbens (NAc) of mice 2 h and 10 days following repeated cocaine administration. In in vitro studies, depletion of Homer1-AS lead to an increase in the corresponding sense gene expression, indicating a potential regulatory mechanisms of Homer1 expression by its corresponding antisense transcript. Future in vivo studies are needed to definitely determine a role for Homer1-AS in cocaine-induced behavioral and molecular adaptations.

天然反义转录本 (NAT) 是一类丰富的长非编码 RNA，最近被证明是神经系统发育和神经系统疾病中染色质动态和基因表达的关键调节因子。然而，目前尚不清楚基于 NAT 的机制是否也在药物诱导的神经适应中发挥作用。基因表达的异常调控是导致物质使用障碍特征的长期行为异常的关键因素之一，并且某些药物诱导的转录反应可能部分是由 NAT 活性的扰动介导的。为了检验这一假设，我们使用了一种自动化算法来挖掘 NCBI AceView 转录组数据库，以识别与成瘾相关的 NAT 重叠基因。我们发现，22% 的检查基因含有 NAT，并且在重复给予可卡因后 2 小时和 10 天，小鼠伏隔核 (NAc) 中Homer1天然反义转录物 ( Homer1-AS ) 的表达发生了改变。在体外研究中， Homer1-AS的缺失导致相应有义基因表达的增加，表明Homer1表达通过其相应反义转录本的潜在调节机制。未来需要体内研究来明确确定Homer1-AS在可卡因诱导的行为和分子适应中的作用。