Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System

Abstract

Substance use disorders (SUD) may emerge from an individual’s attempt to limit negative affective states and symptoms linked to stress. Indeed, SUD is highly comorbid with chronic stress, traumatic stress, or post-traumatic stress disorder (PTSD), and treatments approved for each pathology individually often failed to have a therapeutic efficiency in such comorbid patients. The kappa-opioid receptor (KOR) and its endogenous ligand dynorphin (DYN), seem to play a key role in the occurrence of this comorbidity. The DYN/KOR function is increased either in traumatic stress or during drug use, dependence acquisition and DYN is released during stress. The behavioural effects of stress related to the DYN/KOR system include anxiety, dissociative and depressive symptoms, as well as increased conditioned fear response. Furthermore, the DYN/KOR system is implicated in negative reinforcement after the euphoric effects of a drug of abuse ends. During chronic drug consumption DYN/KOR functions increase and facilitate tolerance and dependence. The drug-seeking behaviour induced by KOR activation can be retrieved either during the development of an addictive behaviour, or during relapse after withdrawal. DYN is known to be one of the most powerful negative modulators of dopamine signalling, notably in brain structures implicated in both reward and fear circuitries. KOR are also acting as inhibitory heteroreceptors on serotonin neurons. Moreover, the DYN/KOR system cross-regulate with corticotropin-releasing factor in the brain. The sexual dimorphism of the DYN/KOR system could be the cause of the gender differences observed in patients with SUD or/and traumatic stress-related pathologies. This review underlies experimental and clinical results emphasizing the DYN/KOR system as common mechanisms shared by SUD or/and traumatic stress-related pathologies, and suggests KOR antagonist as a new pharmacological strategy to treat this comorbidity.

Pain-related behavioral and electrophysiological actions of dynorphin A (1-17)

“…The light-dark maze has not been used in a study of behavioral effects of dynorphin, although the anxiogenic effects of dynorphin have been studied using other measures, such as elevated plus maze, open field test, and forced swim tests. 31 Our results are consistent with this previous work.…”

Posttraumatic Stress Disorder, Suicidal Behavior, Substance Use, and Sexual Victimization Among Adolescent Girls Aged 10-19 Years Living Under Ethnic-Based Civil War in Ethiopia

“…33 , 72 The another possible explanation could be that adolescent girls exposed to PTSD might use alcohol to cope with unpleasant emotional symptoms such as flashbacks, intrusive thoughts, sleep disturbances, concentration problems, and aggressive or irritable reactions towards others. 65 , 67 …”

“…As a result, traumatized women might consume khat to deal with trauma-related negative emotional conditions. [64][65][66][67] In addition, posttraumatic stress disorder was more common among adolescent girls who had suicidal ideation or attempts when compared with their counterparts. This finding was supported by studies done in other countries among adolescents.…”

“…33,72 The another possible explanation could be that adolescent girls exposed to PTSD might use alcohol to cope with unpleasant emotional symptoms such as flashbacks, intrusive thoughts, sleep disturbances, concentration problems, and aggressive or irritable reactions towards others. 65,67 Finally, victims were referred to mental health centers, and since majority of perpetrators were armed, it was very difficult to catch them. We did, however, report any child abuse to the children and women affairs office, which was in charge of legal issues involving child and women abuse.…”

The Acceptability and Feasibility of a Virtual Mantram Program for Patients with Posttraumatic Stress Disorder and Substance Use Disorders: Mixed Method results

“…Among patients diagnosed with PTSD, the prevalence of comorbid substance uses ranges from 19-35%, and some substances (e.g., alcohol), ranges from 36-52% (3). Several causal pathways and theoretical models have been studied to explain the bidirectional relationship between PTSD and SUD, subjecting individuals with PTSD to develop SUD and vice versa (4,5). While approximately half of individuals seeking SUD treatment meet the criteria for current PTSD, these individuals tend to have poorer treatment outcomes compared to those without such comorbidity (6).…”