Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov:130:61-80.
doi: 10.1016/j.neubiorev.2021.08.016. Epub 2021 Aug 17.

A systems omics-based approach to decode substance use disorders and neuroadaptations

Avinash Veerappa  1 , Gurudutt Pendyala  2 , Chittibabu Guda  3
Affiliations
Review

A systems omics-based approach to decode substance use disorders and neuroadaptations

Avinash Veerappa et al. Neurosci Biobehav Rev. 2021 Nov.

Abstract

Substance use disorders (SUDs) are a group of neuropsychiatric conditions manifesting due to excessive dependence on potential drugs of abuse such as psychostimulants, opioids including prescription opioids, alcohol, inhalants, etc. Experimental studies have generated enormous data in the area of SUDs, but outcomes from such data have remained largely fragmented. In this review, we attempt to coalesce these data points providing an important first step towards our understanding of the etiology of SUDs. We propose and describe a 'core addictome' pathway that behaves central to all SUDs. Besides, we also have made some notable observations paving way for several hypotheses; MECP2 behaves as a master switch during substance use; five distinct gene clusters were identified based on respective substance addiction; a central cluster of genes serves as a hub of the addiction pathway connecting all other substance addiction clusters. In addition to describing these findings, we have emphasized the importance of some candidate genes that are of substantial interest for further investigation and serve as high-value targets for translational efforts.

Keywords: Addiction; Addiction pathway; Alcohol; Drug abuse; Genetics; Hallucinogens; Opiates; Psychostimulants; Sedatives; Substance use disorders.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interests

None.

Figures

Figure 1.
Figure 1.
A. Brain reward pathway showing the flow of information from the VTA to the NAc and the prefrontal cortex. The mesocorticolimbic system shown here consists of dopaminergic neurons that are activated by the addictive drugs. B and C show the release, intake, and uptake mechanism of dopamine during normal release and dependence release. D lists addictive agents that alter the release, intake and uptake mechanism of dopamine.
Figure 2.
Figure 2.
The top panel shows an overview of epigenetic regulation beginning from the ligand-binding substances to their corresponding receptors followed by a downstream cascade of gene regulation. The bottom panel shows gradual experience-based neuroadaptations for addiction and the final stage of strong synapse formation from addiction memory pruning.
Figure 3.
Figure 3.
The core addiction pathway displaying distinct substance-induced activity of molecular players promoting reward, motivation, learning, and memory behavior gradually leading to the addictive state, while stimulating drug-seeking acts of craving, binge, and withdrawal.
See this image and copyright information in PMC

References

    1. Agrawal A, Edenberg HJ, Foroud T, Bierut LJ, Dunne G, Hinrichs AL, … Dick DM (2006). Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample. Behav Genet, 36(5), 640–650. doi:10.1007/s10519-006-9069-4 - DOI - PubMed
    1. Agrawal A, Hinrichs AL, Dunn G, Bertelsen S, Dick DM, Saccone SF, … Bierut LJ (2008). Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Drug Alcohol Depend, 93(1–2), 12–20. doi:10.1016/j.drugalcdep.2007.08.015 - DOI - PMC - PubMed
    1. Agrawal A, & Lynskey MT (2009). Candidate genes for cannabis use disorders: findings, challenges and directions. Addiction, 104(4), 518–532. doi:10.1111/j.1360-0443.2009.02504.x - DOI - PMC - PubMed
    1. Agrawal A, Morley KI, Hansell NK, Pergadia ML, Montgomery GW, Statham DJ, … Lynskey MT (2008). Autosomal linkage analysis for cannabis use behaviors in Australian adults. Drug Alcohol Depend, 98(3), 185–190. doi:10.1016/j.drugalcdep.2008.05.009 - DOI - PMC - PubMed
    1. Agrawal A, Pergadia ML, Balasubramanian S, Saccone SF, Hinrichs AL, Saccone NL, … Madden PA (2009). Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerstrom Test for Nicotine Dependence. Addiction, 104(3), 471–477. doi:10.1111/j.1360-0443.2008.02445.x - DOI - PMC - PubMed

Publication types