Epigenetics and memory: causes, consequences and treatments for post‐traumatic stress disorder and addiction

Abstract

Understanding the interaction between fear and reward at the circuit and molecular levels has implications for basic scientific approaches to memory and for understanding the etiology of psychiatric disorders. Both stress and exposure to drugs of abuse induce epigenetic changes that result in persistent behavioral changes, some of which may contribute to the formation of a drug addiction or a stress-related psychiatric disorder. Converging evidence suggests that similar behavioral, neurobiological and molecular mechanisms control the extinction of learned fear and drug-seeking responses. This may, in part, account for the fact that individuals with post-traumatic stress disorder have a significantly elevated risk of developing a substance use disorder and have high rates of relapse to drugs of abuse, even after long periods of abstinence. At the behavioral level, a major challenge in treatments is that extinguished behavior is often not persistent, returning with changes in context, the passage of time or exposure to mild stressors. A common goal of treatments is therefore to weaken the ability of stressors to induce relapse. With the discovery of epigenetic mechanisms that create persistent molecular signals, recent work on extinction has focused on how modulating these epigenetic targets can create lasting extinction of fear or drug-seeking behavior. Here, we review recent evidence pointing to common behavioral, systems and epigenetic mechanisms in the regulation of fear and drug seeking. We suggest that targeting these mechanisms in combination with behavioral therapy may promote treatment and weaken stress-induced relapse.

Animal models for posttraumatic stress disorder: An overview of what is used in research

“…These findings support the hypothesis that deficient endocannabinoid signalling forms a component of PTSD's glucocorticoid dysregulation [9] . While it is generally accepted that HPA function is altered, often assessed as increased cortisol suppression with the dexamethasone challenge, the exact relationship between PTSD and HPA function remains under discussion [10] . Hyper-responsiveness of glucocorticoid receptors is also suggested by the increased circulating and cerebrospinal fluid concentrations of corticotropin releasing factor (CRF) neurotransmitter in PTSD patients, as well as depression and other mood disorders [11] .…”

Stress im Erbgut

“…So bewirken psychische Traumata nicht nur Veränderungen an den Glukokortikoidrezeptoren im Gehirn, sondern stören auch die Genmethylierung in Hippocampus und Amygdala. Dies vermindert die Fähigkeit, sich bei Stress wieder schnell einzuregulieren [2].…”

“…So verändern chronischer Stress oder Traumaerfahrungen die RNA-Aktivität in den Spermien. Man geht davon aus, dass die entsprechend veränderten Informationen nach der Befruchtung an die Eizelle weitergeben werden [2]. Auch diese erfährt unter Traumaeinfluss epigenetische Veränderungen, die an das Kind übergehen.…”

Childhood Trauma, Cognitive Emotion Regulation and Motivation for Behavior Change Among Clients of Opioid Substitution Treatment With and Without Past Year Synthetic Cathinone Use During Therapy

“…Furthermore, as both pathologies can be interpreted as the outcomes of hyperactivity to reminding cues, some argues that PTSD and SUD are in fact disorders of memory (Gisquet-Verrier and Le Dorze, 2019). Exposure to either stress or psychoactive substances can induce epigenetic alterations resulting in similar neurobiological, molecular and behavioral changes (e.g., glucocorticoids can induce excitation patterns by activating dopamine neurons) that facilitate drug-seeking behavior (Pizzimenti and Lattal, 2015). However, experiencing traumatic events does not necessarily lead to PTSD.…”