<i>N</i>‐Acetylcysteine treatment during acute stress prevents stress‐induced augmentation of addictive drug use and relapse

García‐Keller, Constanza; Smiley, Cora E.; Monforton, Cara; Melton, Samantha; Kalivas, Peter W.; Gass, Justin T.

doi:10.1111/adb.12798

Cited by 31 publications

(20 citation statements)

References 46 publications

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“…Other preclinical studies have also shown similar effects on anxiety-like behavior and proinflammatory cytokine expression within the brain using COX-2 inhibitors (Gamble-George et al, 2016;Lee et al, 2016), and human studies suggest that anti-inflammatory treatments such as COX-2 inhibitors may be effective in reducing depression symptoms (Köhler et al, 2014). Interestingly, the antioxidant N-acetylcysteine (NAC) was recently shown to inhibit conditioned stress-induced cocaine and alcohol seeking when administered during or immediately following restraint stress (Garcia-Keller et al, 2020), which raises the question as to whether suppression of oxidative stress and inflammation via NAC treatment is therapeutic in this context. Importantly, NAC is currently being investigated clinically for its use in treating comorbid AUDs and PTSD (Back et al, 2020).…”

Section: Posttraumatic Stress Disordermentioning

confidence: 95%

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

et al. 2021

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Recent studies examining the neurobiology of substance abuse have revealed a significant role of neuroimmune signaling as a mechanism through which drugs of abuse induce aberrant changes in synaptic plasticity and contribute to substance abuse-related behaviors. Immune signaling within the brain and the periphery critically regulates homeostasis of the nervous system. Perturbations in immune signaling can induce neuroinflammation or immunosuppression, which dysregulate nervous system function including neural processes associated with substance use disorders (SUDs). In this review, we discuss the literature that demonstrates a role of neuroimmune signaling in regulating learning, memory, and synaptic plasticity, emphasizing specific cytokine signaling within the central nervous system. We then highlight recent preclinical studies, within the last 5 years when possible, that have identified immune mechanisms within the brain and the periphery associated with addiction-related behaviors. Findings thus far underscore the need for future investigations into the clinical potential of immunopharmacology as a novel approach toward treating SUDs. Considering the high prevalence rate of comorbidities among those with SUDs, we also discuss neuroimmune mechanisms of common comorbidities associated with SUDs and highlight potentially novel treatment targets for these comorbid conditions. We argue that immunopharmacology represents a novel frontier in the development of new pharmacotherapies that promote long-term abstinence from drug use and minimize the detrimental impact of SUD comorbidities on patient health and treatment outcomes.

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Section: Posttraumatic Stress Disordermentioning

confidence: 95%

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

et al. 2021

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“…N-Acetylcysteine (NAC), a precursor of L-cysteine and the antioxidant glutathione (GSH), is found in plants, especially the onion [96][97][98]. NAC has been used as an adjuvant therapy in many psychiatric disorders (e.g., Alzheimer´s disease, schizophrenia, autism, addiction, substance abuse, obsessive-compulsive and mood disorders [24,[99][100][101][102][103][104]), with promising results and no relevant side effects after its administration against inflammation [97]. The use of NAC in a chronic unpredictable mild-stress animal model inhibited the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the hippocampus and prefrontal cortex and exhibited antidepressant-like effects [71].…”

Section: N-acetylcysteine Decreases Inflammatory Responsementioning

confidence: 99%

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

et al. 2020

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Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been associated with an increase in inflammation and oxidative stress. This review presents an overview of findings following antioxidant treatment for ADHD and describes the potential amelioration of inflammation and oxidative stress using antioxidants that might have a future as multi-target adjuvant therapy in ADHD. The use of antioxidants against inflammation and oxidative conditions is an emerging field in the management of several neurodegenerative and neuropsychiatric disorders. Thus, antioxidants could be promising as an adjuvant ADHD therapy.

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“…A recent preclinical study in an animal model of comorbid post-traumatic stress disorder and SUDs showed that NAC could be used prophylactically to prevent or reverse the vulnerability to undergo stressinduced escalation of alcohol use and conditioned stress-induced alcohol (57).…”

Section: Alcohol and N-acetylcysteinementioning

confidence: 99%

N-acetylcysteine in the treatment of substance use disorders

Evren¹

2020

Dusunen Adam

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N-acetylcysteine (NAC) is an agent best known for its clinical efficacy in bronchopulmonary disorders due to its mucolytic properties, and in the treatment of acetaminophen overdose. Given the strong clinical evidence from animal studies of its critical role in regulating glutamatergic receptors, NAC has also been the subject of research related to several psychiatric disorders as a promising treatment approach. This editorial is a brief discussion of the characteristics of NAC and its place in substance use disorders and other psychiatric disorders.

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N‐Acetylcysteine treatment during acute stress prevents stress‐induced augmentation of addictive drug use and relapse

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 31 publications

References 46 publications

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

N-acetylcysteine in the treatment of substance use disorders

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