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https://www.readbyqxmd.com/read/27469021/n-acetylcysteine-amide-ad4-reduces-cocaine-induced-reinstatement
#1
Joanna Jastrzębska, Malgorzata Frankowska, Malgorzata Filip, Daphne Atlas
RATIONALE: Chronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts...
September 2016: Psychopharmacology
https://www.readbyqxmd.com/read/26823954/cardiovascular-and-hepatic-toxicity-of-cocaine-potential-beneficial-effects-of-modulators-of-oxidative-stress
#2
REVIEW
Manuela Graziani, Letizia Antonilli, Anna Rita Togna, Maria Caterina Grassi, Aldo Badiani, Luciano Saso
Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/26592462/n-acetylcysteine-facilitates-self-imposed-abstinence-after-escalation-of-cocaine-intake
#3
Eric Ducret, Mickaël Puaud, Jérôme Lacoste, Aude Belin-Rauscent, Maxime Fouyssac, Emilie Dugast, Jennifer E Murray, Barry J Everitt, Jean-Luc Houeto, David Belin
BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation...
August 1, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/26089997/the-role-of-n-acetylcysteine-in-inhibiting-responding-during-extinction-in-rats-trained-to-self-administer-cocaine
#4
Steven D LaRowe, Peter W Kalivas
Previous work has found that N-acetylcysteine inhibits extinction responding in rats trained to self-administer heroin. The current study examined the ability of N-acetylcysteine to inhibit extinction responding in rats trained to self-administer cocaine. Rats were trained to self-administer cocaine (0.39mg/kg) for 10 to 12 days and were pretreated with either N-acetylcysteine (60mg/kg) or saline beginning on the first day of extinction training and on each extinction training day thereafter. Results indicated that chronically administered N-acetylcysteine reduced lever pressing during extinction sessions...
2010: Open Addiction Journal
https://www.readbyqxmd.com/read/26022265/glutamate-transporter-glt-1-as-a-therapeutic-target-for-substance-use-disorders
#5
REVIEW
Douglas J Roberts-Wolfe, Peter W Kalivas
The development of new treatments for substance use disorders requires identification of targetable molecular mechanisms. Pathology in glutamatergic neurotransmission system in brain reward circuitry has been implicated in relapse to multiple classes of drugs. Glutamate transporter 1 (GLT-1) crucially regulates glutamatergic signaling by removing excess glutamate from the extrasynaptic space. The purpose of this review is to highlight the effects of addictive drug use on GLT-1 and glutamate uptake, and using GLT-1 as a target in addiction pharmacotherapy...
2015: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/25957927/clinical-trials-of-n-acetylcysteine-in-psychiatry-and-neurology-a-systematic-review
#6
REVIEW
Deepmala, John Slattery, Nihit Kumar, Leanna Delhey, Michael Berk, Olivia Dean, Charles Spielholz, Richard Frye
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy...
August 2015: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/25805996/ceftriaxone-and-cefazolin-attenuate-the-cue-primed-reinstatement-of-alcohol-seeking
#7
Ana Weiland, Steven Garcia, Lori A Knackstedt
Alcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of glutamate while the antibiotic cefazolin (CEFAZ) modulates GABA signaling without affecting glutamate. Here, we used the extinction-reinstatement model of relapse to test the ability of these compounds to attenuate the reinstatement of alcohol-seeking...
2015: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/25771148/n-acetylcysteine-prevents-behavioral-and-biochemical-changes-induced-by-alcohol-cessation-in-rats
#8
Ricardo Schneider, Carolina Ferreira Santos, Vanessa Clarimundo, Carla Dalmaz, Elaine Elisabetsky, Rosane Gomez
N-acetylcysteine (NAC), a glutamate-modulating agent with antioxidant and anti-inflammatory properties, has been considered as a potential anti-addictive drug. Beneficial effects were reported for cocaine, cannabis, and tobacco addicts, but the effect of NAC in alcoholics or in alcohol animal models is unknown. The aggravation of alcohol withdrawal symptoms, such as anxiety, has been associated with increased levels of serum corticosterone and leptin. Thus, the aim of this study was to assess the effects of NAC on anxiety, as well as corticosterone and leptin serum levels, after cessation of chronic alcohol treatment in rats...
May 2015: Alcohol
https://www.readbyqxmd.com/read/25720821/n-acetyl-s-n-n-diethylcarbamoyl-cysteine-in-rat-nucleus-accumbens-medial-prefrontal-cortex-and-in-rat-and-human-plasma-after-disulfiram-administration
#9
Robert D Winefield, Anthonius A M Heemskerk, Swetha Kaul, Todd D Williams, Michael J Caspers, Thomas E Prisinzano, Elinore F McCance-Katz, Craig E Lunte, Morris D Faiman
Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain...
March 25, 2015: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/25556383/the-efficacy-of-n-acetylcysteine-in-the-treatment-of-methamphetamine-dependence-a-double-blind-controlled-crossover-study
#10
RANDOMIZED CONTROLLED TRIAL
Seyed Ghafur Mousavi, Mohammad Reza Sharbafchi, Mehrdad Salehi, Mohammad Peykanpour, Naeemeh Karimian Sichani, Mohammad Maracy
OBJECTIVE: Preclinical studies and early pilot clinical investigations have suggested that N-acetylcysteine (NAC) may be useful in treatment of methamphetamine (METH) dependence. The present study evaluated whether NAC would suppress craving to the METH. METHODS: In a double-blind, controlled crossover clinical trial, 32 METH-dependent volunteers were chosen to receive either NAC (1200 mg/day) or placebo, randomly. They were intervened in two four-week sessions...
January 2015: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/24676047/systematic-review-of-n-acetylcysteine-in-the-treatment-of-addictions
#11
REVIEW
Elson Asevedo, Ana C Mendes, Michael Berk, Elisa Brietzke
OBJECTIVE: To conduct the first systematic literature review of clinical trials of N-acetylcysteine (NAC) for the treatment of substance abuse disorders and addictive behaviors. METHODS: A search of the MEDLINE, Embase and PsycINFO databases was conducted. The inclusion criteria for the review were clinical trials that used NAC in the treatment of a disorder related to substance use and/or addictive behaviors, limited to texts in English, Spanish, or French. The selected studies were evaluated with respect to type of trial, sample size, diagnostic input, intervention, length of follow-up, outcome variables, and results...
April 2014: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/24613240/the-effects-of-n-acetylcysteine-on-cocaine-reward-and-seeking-behaviors-in-a-rat-model-of-depression
#12
Małgorzata Frankowska, Joanna Jastrzębska, Ewa Nowak, Magdalena Białko, Edmund Przegaliński, Małgorzata Filip
Depression and substance-abuse (e.g., cocaine) disorders are common concurrent diagnoses. In the present study, we combined bilateral olfactory bulbectomy (OBX) with a variety of procedures of intravenous cocaine self-administration and extinction/reinstatement in rats. We also investigated the effects of N-acetylcysteine (NAC) on rewarding and seeking behaviors for cocaine in OBX rats and compared the drug's effects in sham-operated control animals (SHAM). The occurrence of depressive symptoms before introduction to cocaine self-administration enhanced subsequent cocaine-seeking behaviors but did not significantly influence cocaine's rewarding properties or extinction training...
June 1, 2014: Behavioural Brain Research
https://www.readbyqxmd.com/read/24612076/glutamate-transporter-glt-1-mediates-n-acetylcysteine-inhibition-of-cocaine-reinstatement
#13
Kathryn J Reissner, Cassandra D Gipson, Phuong K Tran, Lori A Knackstedt, Michael D Scofield, Peter W Kalivas
Both pre-clinical and clinical studies indicate that N-acetylcysteine (NAC) may be useful in treating relapse to addictive drug use. Cocaine self-administration in rats reduces both cystine-glutamate exchange and glutamate transport via GLT-1 in the nucleus accumbens, and NAC treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by NAC is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of GLT-1 and/or cystine-glutamate exchange is required for NAC to inhibit cue-induced reinstatement of cocaine seeking, we utilized the rat self-administration/extinction/reinstatement model of cocaine relapse...
March 2015: Addiction Biology
https://www.readbyqxmd.com/read/24531561/effects-of-repeated-cocaine-exposure-on-habit-learning-and-reversal-by-n-acetylcysteine
#14
Laura H Corbit, Billy C Chieng, Bernard W Balleine
Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively...
July 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24442756/potential-role-of-n-acetylcysteine-in-the-management-of-substance-use-disorders
#15
REVIEW
Erin A McClure, Cassandra D Gipson, Robert J Malcolm, Peter W Kalivas, Kevin M Gray
There is a clear and pressing need to expand pharmacotherapy options for substance use disorders (SUDs) in order to improve sustained abstinence outcomes. Preclinical literature has demonstrated the role of glutamate in addiction, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. Glutamatergic agents for SUDs may span multiple addictive behaviors and help demonstrate potentially overlapping mechanisms in addiction. The current review will focus specifically on N-acetylcysteine (NAC), a safe and well-tolerated glutamatergic agent, as a promising potential pharmacotherapy for the treatment of SUDs across several substances of abuse...
February 2014: CNS Drugs
https://www.readbyqxmd.com/read/24212597/cocaine-induced-agitated-delirium-a-case-report-and-review
#16
REVIEW
Theodore Plush, Walter Shakespeare, Dorian Jacobs, Larry Ladi, Sheeba Sethi, James Gasperino
Cocaine use continues to be a major public health problem in the United States. Although many of the initial signs and symptoms of cocaine intoxication result from increased stimulation of the sympathetic nervous system, this condition can present as a spectrum of acuity from hypertension and tachycardia to multiorgan system failure. Classic features of acute intoxication include tachycardia, arterial vasoconstriction, enhanced thrombus formation, mydriasis, psychomotor agitation, and altered level of consciousness...
January 2015: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/24112049/covalent-thiol-adducts-arising-from-reactive-intermediates-of-cocaine-biotransformation
#17
Kevin J Schneider, Anthony P DeCaprio
Exposure to cocaine results in the depletion of hepatocellular glutathione and macromolecular protein binding in humans. Such cocaine-induced responses have generally been attributed to oxidative stress and reactive metabolites resulting from oxidative activation of the cocaine tropane nitrogen. However, little conclusive data exists on the mechanistic pathways leading to protein modification or the structure and specificity of cocaine-derived adduction products. We now report a previously uncharacterized route of cocaine bioactivation leading to the covalent adduction of biological thiols, including cysteine and glutathione...
November 18, 2013: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/24109187/role-of-nucleus-accumbens-glutamatergic-plasticity-in-drug-addiction
#18
REVIEW
Gabriel C Quintero
Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance's effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences...
2013: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/23985782/chronic-administration-of-the-methylxanthine-propentofylline-impairs-reinstatement-to-cocaine-by-a-glt-1-dependent-mechanism
#19
Kathryn J Reissner, Robyn M Brown, Sade Spencer, Phuong K Tran, Charles A Thomas, Peter W Kalivas
In recent years, interactions between neurons and glia have been evaluated as mediators of neuropsychiatric diseases, including drug addiction. In particular, compounds that increase expression of the astroglial glutamate transporter GLT-1 (N-acetylcysteine and ceftriaxone) can decrease measures of drug seeking. However, it is unknown whether the compounds that influence broad measures of glial physiology can influence behavioral measures of drug relapse, nor is it clear whether the upregulated GLT-1 is functionally important for suppressing of drug seeking...
January 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/23952889/a-double-blind-placebo-controlled-trial-of-n-acetylcysteine-in-the-treatment-of-cocaine-dependence
#20
RANDOMIZED CONTROLLED TRIAL
Steven D LaRowe, Peter W Kalivas, Joyce S Nicholas, Patrick K Randall, Pascale N Mardikian, Robert J Malcolm
BACKGROUND: There remains no FDA approved medication for the treatment of cocaine dependence. Preclinical studies and early pilot clinical investigations have suggested that N-acetylcysteine (NAC) may be useful in the treatment of the disorder. OBJECTIVE: The present report assessed the efficacy of NAC in the treatment of cocaine dependence. METHODS: Cocaine-dependent volunteers (n = 111) were randomized to receive daily doses of 1,200 mg of NAC, 2,400 mg of NAC, or placebo...
September 2013: American Journal on Addictions
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