Long-Noncoding RNA Gas5 Is Associated with Drug Addiction

Long non-coding RNAs (lncRNAs) are a class of transcribed RNA molecules greater than 200 nucleotides long that do not encode proteins. Recently, many lncRNAs have been recognized to be functionally important, particularly with respect to the regulation of gene expression. Though lncRNAs are abundant in the brain, their neural functions are largely unknown. Here we show that the lncRNA growth arrest-specific 5 (Gas5) is downregulated in the mouse nucleus accumbens (NAc) both 1 and 24 hours after 7 daily cocaine intraperitoneal injections. Furthermore, Gas5 downregulation is maintained 10 days after 28 days of cocaine administration. Gas5 is known to negatively regulate cell survival and is aberrantly expressed in several cancers. However, its role in neural functions is unclear. Accumulating evidence suggests that Gas5 may prevent the glucocorticoid receptor from interacting with the glucocorticoid response element, and thereby suppresses glucocorticoid downstream nuclear signaling. In order to elucidate the role of Gas5 in drug action, we incorporated Gas5 into a herpes simplex viral vector and overexpressed it in the mouse nucleus accumbens through steretotaxic surgery injection. Our preliminary data demonstrate that Gas5 overexpression significantly decreases drug preference during conditioned place preference (CPP). As the glucocorticoid receptor is implicated in drug addiction, further study of Gas5 may provide a novel molecular underpinning of drug addiction linked to the glucocorticoid receptor signaling pathway.