Editorial [Hot Topic: Drug Addiction and Brain Targets: From Preclinical Research to Pharmacotherapy (Guest Editor: Shafiqur Rahman)]

Drug addiction is a complex neurological disorder affecting millions of people around the world [1]. This relapsing disease not only affects the individual, but also their family and community at large with severe medical and economic consequences [2]. In the past decades, groundbreaking scientific discoveries about the brain have revolutionized our understanding of drug addiction, enabling us to respond more effectively to the disease [3]. Current scientific information on the neurobiology of drug addiction has expanded significantly and the number of technological breakthroughs has also increased our understanding about the pathophysiology of drug addiction [1, 3]. However, limitations exist on the therapeutic frontier for treatment of many forms of drug addiction and abuse as current medications are not fully efficacious or devoid of side effects that limit compliance. Moreover, therapeutic strategies are not currently available for all forms of drug addiction. Thus, there is a need to translate the current knowledge derived from preclinical research into the discovery and development of effective and safe pharmacotherapeutic strategies. This hot topic issue, Drug Addiction and Brain Targets from Preclinical Research to Pharmacotherapy, consists of seven reviews written by eminent experts in the field. The issue covers important aspects of neuroscience research on drug addiction associated with the primary central nervous system neurotransmitter receptors implicated in drug addiction. The reviews in this themed issue describe some of the latest concepts in preclinical research, analyze breakthrough findings, define approaches and target multiple brain substrates including, dopamine transporters, dopamine D3 receptors, neuronal nicotinic receptors, opioid receptors, serotonergic (5-HT3) receptors, cannabinoid receptors and the glutamate receptor system for discovery of medications for the clinical management of drug addictions. Zhu and Reith have provided an extensive description of the dopamine transporter as an important target for the central nervous system actions of psychostimulants, nicotine, and other drugs of abuse such as ethanol, heroin, and morphine. They focus their review on multiple factors that regulate dopamine transporter function associated with reinforcing effects of psychostimulants and other classes of abused drugs. They also discuss current research on dopamine transporter activity in relation to novel environmental factors that might be critical to psychostimulant abuse. The latest findings on dopamine transporter function highlighted in this review provide a solid framework for understanding effects of commonly abused drugs related to dopamine transporter function. Implications of this scientific insight for the discovery of novel anti-addiction medications are discussed. Heidbreder reviews preclinical evidence that selective antagonism of dopamine D3 receptors are a viable potential target for drug addiction pharmacotherapy. The author has provided a comprehensive review focused on dopamine D3 receptor expression in the rodent and human brain, changes in expression of the dopamine D3 receptor following exposure to drugs of abuse, and efficacy of selective dopamine D3 receptor antagonists in preclinical models assessing the abuse-related behavioral effects of drugs such as cocaine, nicotine, alcohol, methamphetamine and heroin. The translational value of the extensive preclinical work reviewed in this article provides great value in understanding both the function of this dopamine receptor subtype in the actions of abused drugs and the potential of antagonists of this site for the therapeutic management of addictive disorders. Rahman et al. have described the important role of brain nicotinic receptors as potential targets for pharmacotherapy of nicotine addiction and other addictive disorders. The authors discuss the heterogeneity of brain nicotinic receptors and their function in the presence of nicotine. They cover the potential role of nicotinic receptors in mediating nicotine-induced addictive behavior in preclinical models. Current knowledge and understanding on the neurochemical basis of nicotine and other forms of drug addiction are also discussed. The progress and latest lines of research in the nicotinic receptor field reviewed in this chapter shed new light for future translational research and act as platform for therapeutic discovery in the management of nicotine and other forms of drug addiction, including alcoholism. Shippenberg et al. focus their review on mu-and delta-opioid receptors as targets for the treatment of opiate and other drug addiction. The authors discuss critical roles of mu-opioid and delta opioid receptors in mediating the rewarding effects produced by several classes of abused drugs. They also review the potential contribution of delta opioid receptors to mu opioid receptor function in various drug addiction processes. This comprehensive review highlights and documents the functional interactions of mu-opioid receptor and delta-opioid receptor as new targets for the treatment of opiate and psychostimulant addiction. Thus, in addition to discussing current data on these important molecular mechanisms of drug action, this chapter also provides a data-based understanding of the use of these mechanisms for defining strategies for the discovery of new opiate analgesics with reduced side effects.