Coinciding revolutions: how discovery of non-coding DNA and RNA can change our understanding of addiction.

The twenty-first century started with the Big Bang—the first ever sequencing of the human genome in 2000/2003 (Lander et al., 2001; Venter, 2003), and since then our scientific Universe started to expand with the speed of light. This year (2012) the Supernova exploded—the Encode project, a series of thirty papers, trashed the “junk DNA” concept. The project indicates that the vast majority (99%) of the human genome, although non-coding, is not “junk” but is biologically active and essential to maintain fundamental processes in a cell (Bernstein et al., 2012). One of the earlier stellar breakthroughs was the discovery of microRNA, a short RNA species crucial for regulation of gene expression (Lee et al., 1993). With discoveries like these, it becomes more and more obvious that our biological Universe is much more complex and dynamic than we have ever imagined. It is very probable that many biological rules and regulations still await discovery. This is particularly important for our understanding of the mechanisms underlying the development of chronic diseases, like addiction. Addiction is a persistent, neurobiological disease affecting primarily the brain’s reward system, which consists of a circuitry of several interconnecting brain regions, including the prefrontal cortex, nucleus accumbens, ventral tegmental area, amygdala, paraventricular nucleus, and others (Koob and Le Moal, 2001). The reward system is one of the most important physiological features of the brain. We use it constantly, unconsciously, to make countless decisions essential to complete simple and complex tasks, by performing risk/benefit ratio analyses. This powerful motivator drives human and animal behavior, allows an individual to thrive and ultimately, for a species to propagate. Some drugs target the reward system and can drastically change the behavior of individuals vulnerable to addiction, which is characterized as the refocusing of all activities on one goal— the continued intake of the drug. The drug’s effect on the CNS is so powerful that the individual will continue to use it despite any associated adverse consequences. Neurobiological models of addiction try to explain how chronic or frequent exposure to addictive drugs hijacks the elements of the brain reward circuitry and causes transition from voluntary drug-taking to habitual and compulsive drug-seeking (Hyman and Malenka, 2001). During this transition, neuronal adaptations occur, which perpetuate and intensify the disease. Escalating drug intake due to tolerance causes incessant transition of the allostatic set-point, which fails to maintain system stability. Usually, drug addiction and alcohol addiction are described separately, but at the biological level both addictions have common core changes in the reward system through similar neuronal adaptations. However, in either type of addiction, many molecular underpinnings are still unknown. Recently, several papers described the involvement of different non-coding RNAs, primarily microRNA, in unraveling novel molecular mechanisms of this debilitating disease. We put together this Special Issue of Frontiers in Genetics to provide our readers with a comprehensive overview of current research on non-coding RNA in both drug and alcohol addiction. We invited leaders in this dynamic new field to write a series of reviews, and other prominent scientists to share their views of this subject through a series of editorials. This special issue is divided into five chapters: alcohol, nicotine, cocaine, morphine, and bioinformatics. Alcohol is a simple product of yeast fermentation, and is fairly easy to obtain. People have been using alcohol probably from the beginning of recorded history. Alcohol addiction (alcoholism) is the oldest and most widespread type of addiction. In this special issue, Nunez and Mayfield (2012) describe microRNA signatures in the brains of alcoholics and the process of microRNA modulation of epigenetic nuclear mechanisms. Miranda (2012) discusses teratological consequences of microRNA disregulation by alcohol during fetal development. The editorial by Reilly (2012) explains how studying microRNA can provide new perspectives and treatments of alcoholism and Fetal Alcohol Spectrum Disorder (FASD). Nicotine is primarily inhaled during the smoking of dried tobacco leaves (Nicotiana tabacum), but also can be consumed in other forms. Nicotine addiction has spread quickly around the world in the post-Columbian era, becoming a major, presentday health issue in many countries. According to Maccani and Knopik (2012), detrimental effects of nicotine start very early— in utero. They describe in their review how maternal cigarette smoking during pregnancy alters expression of selected microRNAs in placenta. They also discuss the effect of cigarette smoking onmicroRNA and long non-coding RNA (lncRNA) expression in the epithelium of airways, which is important in the pathogenesis of cancer. Their review indicates that environmentally regulated epigenetic changes affect health throughout the course of one’s life, while an editorial by Ehringer (2012) describes the presence of “critical periods” during which the environmental effect is particularly strong. Morphine is the most abundant alkaloid found in opium (opiate), a product of the poppy fruit (Papaver somniferum). Morphine has been used for centuries to treat pain. However, morphine and related products have very potent addictive properties. Currently, addiction to morphine and related drugs is rising, mainly in affluent countries. Several microRNAs have been shown to be important in morphine actions. In this Special Issue,