Chronic Stress, Drug Use, and Vulnerability to Addiction

Abstract

Stress is a well-known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population-based and epidemiological studies have identified specific stressors and individual-level variables that are predictive of substance use and abuse. Preclinical research also shows that stress exposure enhances drug self-administration and reinstates drug seeking in drug-experienced animals. The deleterious effects of early life stress, child maltreatment, and accumulated adversity on alterations in the corticotropin releasing factor and hypothalamic-pituitary-adrenal axis (CRF/HPA), the extrahypothalamic CRF, the autonomic arousal, and the central noradrenergic systems are also presented. The effects of these alterations on the corticostriatal-limbic motivational, learning, and adaptation systems that include mesolimbic dopamine, glutamate, and gamma-amino-butyric acid (GABA) pathways are discussed as the underlying pathophysiology associated with stress-related risk of addiction. The effects of regular and chronic drug use on alterations in these stress and motivational systems are also reviewed, with specific attention to the impact of these adaptations on stress regulation, impulse control, and perpetuation of compulsive drug seeking and relapse susceptibility. Finally, research gaps in furthering our understanding of the association between stress and addiction are presented, with the hope that addressing these unanswered questions will significantly influence new prevention and treatment strategies to address vulnerability to addiction.

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

“…Specifically, the NAcc of adult rats exposed to GC in utero (iuGC) display reduced neuronal numbers and fewer dopamine (DA) inputs from the VTA (12). Further, early life stress is known to influence DA receptor expression in the adult NAcc (16,17), changes associated with increased behavioral responses to stress and cocaine (1,4,18,19). Together, these observations suggest that prenatal exposure to elevated levels of GCs can program the mesolimbic circuit.…”

“…Stressful events during critical developmental periods have long been considered as etiological factors in psychiatric disorders such as schizophrenia, depression and drugseeking behavior (1)(2)(3)(4). The programming effects of stress are most likely mediated by endogenous glucocorticoids (GC) whose ability to produce structural re-organization and dysfunction of the neural substrates that underpin these stress-related pathologies are well known (1,(5)(6)(7).…”

“…In the present study, a multimodal analysis was used to further define the molecular neurobiological mechanisms that underlie the initiation and reversibility of drug-seeking behavior by prenatal exposure to GCs. 4 …”

Effect of Self-Esteem in the Relationship between Stress and Substance Abuse among Adolescents: A Mediation Outcome

“…Abundant evidence therefore suggest that availability, genetics, personality and social environment all contribute to substance abuse vulnerability among adolescents, with strong evidence revealing the role of stress in the maintenance and sustenance of the phenomenon [5]. Substance abuse occurs most frequently among adolescents Manuscript with stress disorders [6], and stress disorders were related to frequent alcohol usage [7].…”

Non-medical use of prescription drugs by young men: impact of potentially traumatic events and of social-environmental stressors

“…On the other side, long-lasting social-environmental stressors which are not necessarily of traumatic nature were investigated. These stressors are known to be relevant risk factors for developing substance use disorders or NMUPD (Sinha, 2008). In addition to investigating NMPDU as an umbrella behaviour, it is also investigated whether potentially traumatic events and long-lasting environmental stressors are differentially associated with distinct drug classes.…”