The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Cystine/Glutamate Exchange Regulates Metabotropic Glutamate Receptor Presynaptic Inhibition of Excitatory Transmission and Vulnerability to Cocaine Seeking
Open accessAbstract
Withdrawal from chronic cocaine reduces extracellular glutamate levels in the nucleus accumbens by decreasing cystine/glutamate exchange (xc-). Activating xc- with N-acetylcysteine restores extracellular glutamate and prevents cocaine-induced drug seeking. It was hypothesized that the activation of xc- prevents drug seeking by increasing glutamatergic tone on presynaptic group II metabotropic glutamate receptors (mGluR2/3) and thereby inhibiting excitatory transmission. In the first experiment, the capacity of glutamate derived from xc- to regulate excitatory transmission via mGluR2/3 was determined. Physiological levels of cystine (100-300 n m) were restored to acute tissue slices from the nucleus accumbens or prefrontal cortex. Cystine increased glutamate efflux and decreased miniature EPSC (mEPSC) and spontaneous EPSC (sEPSC) frequency as well as evoked EPSC amplitude. These effects of cystine were presynaptic, because there was no change in mEPSC or sEPSC amplitude, and an increase in the evoked EPSC paired-pulse facilitation ratio. The cystine-induced reduction in EPSCs was reversed by blocking either xc- or mGluR2/3. In the second experiment, blocking mGluR2/3 prevented the ability of N-acetylcystine to inhibit the reinstatement of drug seeking in rats trained to self-administer cocaine. These data demonstrate that nonsynaptic glutamate derived from xc- modulates synaptic glutamate release and thereby regulates cocaine-induced drug seeking.
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Cites
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McFarland, K., Lapish, C. C., & Kalivas, P. W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03531.2003 · Cited by 885
Self-citationNeuroadaptations in cystine-glutamate exchange underlie cocaine relapse
Baker, D. A., McFarland, K., Lake, R. W., Shen, H., Tang, X.-C., Toda, S., & Kalivas, P. W. (2003) · Nature Neuroscience · doi:10.1038/nn1069 · Cited by 739
Self-citationUnmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission
Kalivas, P. W., Volkow, N., & Seamans, J. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.005 · Cited by 657
Self-citationThomas, M. J., Beurrier, C., Bonci, A., & Malenka, R. C. (2001) · Nature Neuroscience · doi:10.1038/nn757 · Cited by 629
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Self-citationThe Origin and Neuronal Function of In Vivo Nonsynaptic Glutamate
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Cited by
The Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757
Self-citationThe glutamate homeostasis hypothesis of addiction
Kalivas, P. W. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2515 · Cited by 1,350
Self-citationTargeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
Sanacora, G., Zarate, C. A., Krystal, J. H., & Manji, H. K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2462 · Cited by 894
Extinction circuits for fear and addiction overlap in prefrontal cortex
Peters, J., Kalivas, P. W., & Quirk, G. J. (2009) · Learning & Memory · doi:10.1101/lm.1041309 · Cited by 736
Self-citationDrug Addiction as a Pathology of Staged Neuroplasticity
Kalivas, P. W., & O'Brien, C. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301564 · Cited by 733
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Metadata
- Authors
- Moran, M. M., McFarland, K., Melendez, R. I., Kalivas, P. W., & Seamans, J. K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-07-06
- Volume
- 25
- Issue
- 27
- Pages
- 6389-6393
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2045185962
- Cited by
- 411
- References
- 25
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Moran, M. M., McFarland, K., Melendez, R. I., Kalivas, P. W., & Seamans, J. K. (2005). Cystine/Glutamate Exchange Regulates Metabotropic Glutamate Receptor Presynaptic Inhibition of Excitatory Transmission and Vulnerability to Cocaine Seeking. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.1007-05.2005
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