Aim: The objective of this review is to provide a synthesis of current knowledge of the neurobiological mechanisms underlying vulnerability and resilience in substance use disorders (SUD). Methods: PubMed and PsycINFO database search was conducted from May 1997 until April 2017, for relevant articles outlining the outcomes of case files, control studies and observational studies regarding neurochemical aberrations secondary to drug abuse as well as allostatic processes affecting the course and severity of SUD. Results: The relation between drugs of abuse and the neurobiological milieu seems to be a mutual process; drugs of abuse affect the expression of neurobiological systems, and neurobiological systems affect the manifestation of addiction. The review of current literature outlines the roles of early life experience, allostatic processes and genetic polymorphism, which confer the vulnerable or resilient phenotype in SUD. Human and animal studies have revealed dysregulation and adaptive responses of specific neurochemical mechanisms in the brain reward systems (dopamine, opioid peptides, substance P, GABA, estrogen), the brain stress systems (CRH, cortisol, norepinephrine), the brain anti-stress system (serotonin, DHEA, NYP, endocannabinoids, galanin, oxytocin), as well as glutamate implicated in impulse control and BDNF associated with neuroprotection. Genetic studies suggest roles for the genes encoding the neurochemical elements involved in these neurobiological systems, predisposing to vulnerability and resilience in hedonic biochemical use. Conclusion: Major neurobiological changes in substance abuse disorder common to human and animal studies include a compromised reward system, over activated brain stress systems, compromised anti-stress system as well as compromised impulse control and response inhibition system. Existing data indicate that allostatic processes and genetic polymorphism exert a significant influence on the course and severity of SUD, conferring the vulnerable or resilient phenotype. (c) 2018 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S. L. U. All rights reserved.
