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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2018.00309

Stress as a Risk Factor for Addiction: A Mini-Review of Candidate Molecular Mediators

  • 1Virginia Commonwealth University, United States

A collective review of the existing literature demonstrates that stress can increase susceptibility to drug addiction. Despite a strong correlation between stress and susceptibility, a developed picture of the mechanisms by which stress impacts cocaine dependence via the mesolimbic pathway are not fully defined. In this mini-review, we highlight three mechanisms by which glucocorticoids and the dopaminergic system interact. In light of this interplay, we examine recent literature on cocaine dependence at critical points in the mesolimbic pathway including the ventral tegmental area (VTA) and nucleus accumbens (NAcs). Furthermore, we clarify the role of stress in cocaine dependence at these important points. Taken together, the available literature suggests that stress augments the influence of cocaine addiction at multiple points along the VTA mesolimbic projection and uniquely in the NAcs through a positive feedback mechanism. Further research is required to outline the interaction between the prefrontal cortex (PFC) and key molecular mediators including ΔFosB, CREB, and CDK5 which are highlighted in this mini-review. Ultimately, a more complete understanding of the biological interactions between the circuitry which mediates addiction, and that which responds to stressor exposure, will facilitate the identification of novel prevention and treatment strategies.

Keywords: stress, Addiction, Cocaine, VTA, NAc, drugs

Received: 28 Jun 2018; Accepted: 28 Nov 2018.

Edited by:

James P. Herman, University of Cincinnati, United States

Reviewed by:

Fabio Marti, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Susan Martelle, University of Cincinnati, United States  

Copyright: © 2018 Mukhara and Neigh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Gretchen N. Neigh, Virginia Commonwealth University, Richmond, United States, gretchen.mccandless@vcuhealth.org