Genes and Pathways Co-associated with the Exposure to Multiple Drugs of Abuse, Including Alcohol, Amphetamine/Methamphetamine, Cocaine, Marijuana, Morphine, and/or Nicotine: a Review of Proteomics Analyses

Abstract

Drug addiction is a chronic neuronal disease. In recent years, proteomics technology has been widely used to assess the protein expression in the brain tissues of both animals and humans exposed to addictive drugs. Through this approach, a large number of proteins potentially involved in the etiology of drug addictions have been identified, which provide a valuable resource to study protein function, biochemical pathways, and networks related to the molecular mechanisms underlying drug dependence. In this article, we summarize the recent application of proteomics to profiling protein expression patterns in animal or human brain tissues after the administration of alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine/heroin/butorphanol, or nicotine. From available reports, we compiled a list of 497 proteins associated with exposure to one or more addictive drugs, with 160 being related to exposure to at least two abused drugs. A number of biochemical pathways and biological processes appear to be enriched among these proteins, including synaptic transmission and signaling pathways related to neuronal functions. The data included in this work provide a summary and extension of the proteomics studies on drug addiction. Furthermore, the proteins and biological processes highlighted here may provide valuable insight into the cellular activities and biological processes in neurons in the development of drug addiction.

Proteomic Approaches and Identification of Novel Therapeutic Targets for Alcoholism

“…Nevertheless, owing to the limitations of the methods utilized to date, not all the proteins associated with alcohol exposure have been identified by proteomic technologies. Similar to what has been found for other proteomic studies of addictive disorders (Wang et al, 2011), the majority of identified proteins related to alcohol abuse belong to a relatively small number of functional categories (Figure 1). This is consistent with the observation that some genetic influences may not be specific for alcohol-use disorders, but likely reflect a general vulnerability for polysubstance abuse (Gorini et al, 2011;Mayfield et al, 2008;Nestler, 2005).…”

“…Although the methodologies are continuously evolving, proteomic strategies have already become essential tools for elucidating the molecular effects of addictive substances. In the past decade, the number of laboratories using protein expression profiling to define changes in global proteomes in cultured neurons or different brain regions of animals or humans in response to substances of abuse has been steadily growing (Bierczynska-Krzysik et al, 2006;Hemby and Tannu, 2009;Hemby, 2010;Li and Wang, 2007;Romanova et al, 2012;Song et al, 2012;Wang et al, 2011;Witzmann and Strother, 2004).…”

“…In the past decade, comparison studies of subcellular amounts of transcripts and proteins showed with increasing accuracy that altered mRNA expression does not completely explain changes in protein levels (Baek et al, 2008;Chen et al, 2002;Greenbaum et al, 2003;Guo et al, 2010b;Hendrickson et al, 2009;Schwanhäusser et al, 2011). As a result, the use of proteomic techniques has grown in addiction-related research because of their ability to precisely measure global dynamic modifications in proteomes (Abul-Husn and Devi, 2006;Drabik et al, 2007;Hemby and Tannu, 2009;Li and Wang, 2007;Lull et al, 2010;Marcotte et al, 2003;Plazas-Mayorca and Vrana, 2011;Wang et al, 2011). Similar to other neuropsychiatric addictive disorders, alcoholism engages a considerable collection of protein complexes and is thus suitable for proteomic investigations.…”

Retrotransposition of Long Interspersed Element 1 Induced by Methamphetamine or Cocaine

“…As reported by numerous studies, some cell signaling cascades are activated by METH and cocaine, such as the ERK, phosphatidylinositol 3-kinase, V-akt murine thymoma viral oncogene homolog 1 (Akt-1), and CREB pathways. The transcription factor CREB is often induced after chronic abuse of drugs (42–45). …”

Cannabis Smoking in 2015

“…45 Finally, neuroscientists have begun using proteomics technologies evaluating brain tissue in the context of illicit drug use to demonstrate that cannabis use is associated with oxidative stress and alterations in signal transduction. 46 However, use of proteomics and other omics technologies to establish mechanistic eff ects of cannabis on lung remain virtually unexplored.…”