Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse

By D. Baker, K. McFarland, R. Lake, Hui Shen, Xing-chun Tang, S. Toda, Peter W. Kalivas. Nature Neuroscience, 2003

762 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c383d9697dd46ee589767c4e58833c0781fcc46b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Peter W. Kalivas
2. G. Koob
3. Nora D. Volkow
4. E. Nestler
5. R. Malenka
6. S. Hyman
7. Kent C. Berridge
8. J. Steketee

In Molecular Biology

1. Nora D. Volkow
2. G. Koob
3. R. Malenka
4. Peter W. Kalivas
5. E. Nestler
6. S. Hyman
7. J. Steketee
8. C. O'Brien

Citations in the corpus

• Neurocircuitry of Addiction (2009, background): “This glutamate dysregulation has been hypothesized to be caused by decreased function of the cystine–glutamate exchanger (Baker et al, 2003) and desensitization of the metabotropic glutamate mGlu2/3 receptor.”
• The Cystine/Glutamate Antiporter System xc − in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities (2013, neutral): “It was found that the reduction in extracellular glutamate after chronic treatment with either cocaine or nicotine resulted from reduced system xc - activity and levels of xCT expression in the accumbens (8, 120).”
• Drug Addiction as a Pathology of Staged Neuroplasticity (2008, background): “Key among these molecular adaptations is downregulation of cystine–glutamate exchange (xc ) (Baker et al, 2003). xc is the rate-limiting step whereby cells acquire cystine to make the intracellular antioxidant glutathione, and occurs by exchanging the uptake of one cystine in exchange for the…”
• Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior (2011, background): “This led to experiments demonstrating that restoring basal glutamate levels in the nucleus accumbens could reduce relapse to drug-seeking behavior in animal models and humans (Baker et al., 2003; Mardikian et al., 2007; Zhou and Kalivas, 2008; Knackstedt et al., 2009, 2010; Sari et al., 2009).”
• Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. (2011, background): “This antiporter was recently found to be decreased by repeated cocaine exposure, and restoration of the activity prevented cocaine-primed drug seeking behavior in rats (Baker et al., 2003).”
• The Neuroscience of Drug Reward and Addiction. (2019, neutral): “The latter relies on cellular adaptations leading to reduced levels of extra-cellular glutamate in NAc (12) that might also contribute to compulsive drug seeking.”
• Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? (2015, background): “This allows the brain to maintain a very low extracellular Lglu concentration in the low micromolar range (Baker et al., 2003; De Bundel et al., 2011).”
• Extinction circuits for fear and addiction overlap in prefrontal cortex. (2009, background): “This drug is thought to act by restoring glutamate levels in the accumbens of addicts based on data from rodent studies (Baker et al. 2003).”
• Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure (2006, background): “…that reinstatement of cocaine seeking is attenuated by systemic injections of N-acetylcysteine that result in tonic increases in accumbens glutamate levels in rats (Baker et al. 2003); preliminary results suggest that the same drug attenuates cocaine craving in addicted humans (LaRowe et al. 2006).”
• Mesocorticolimbic Circuits are Impaired in Chronic Cocaine Users as Demonstrated by Resting State Functional Connectivity (2010, positive): “Cellular and molecular studies in animal models of drug dependence show enduring glutamatergic neuroadaptations in the PFC of rats following chronic cocaine administration, and such alterations appear to play a critical role in drug addiction and subsequent relapse to drug-seeking behavior (Baker et”
• Neural mechanisms of addiction: the role of reward-related learning and memory. (2006, background): “Thus, prolonged withdrawal from chronic cocaine decreases activity of the cystine-glutamate transporter in glial cells located within this brain region (Baker et al. 2003).”
• The chemistry and biological activities of N-acetylcysteine. (2013, background): “For example, NAC normalized the levels of glutamate in the nucleus accumbens of cocaine-treated rats [238].”
• Physiology of Astroglia. (2018, neutral): “Genetic deletion of the catalytic subunit of the Sxc led to 50% decrease in extracellular glutamate measured by microdialysis (1080); a similar decrease was observed following chronic administration of cocaine or nicotine known to reduce expression of Sxc (87, 1162).”