Abstract:
BACKGROUND:The cystine-glutamate exchanger is downregulated after chronic cocaine, resulting in reduced extracellular levels of nucleus accumbens glutamate. The importance of cocaine-induced loss of glutamate homeostasis is revealed by N-acetylcysteine restoring cystine-glutamate exchange and attenuating reinstatement to cocaine seeking. Another regulator of extracellular glutamate is the glial glutamate transporter GLT-1. We hypothesized that cocaine self-administration reduces GLT-1 and that GLT-1 upregulation inhibits cocaine seeking. METHODS:We measured [(3)H] glutamate uptake and protein expression of GLT-1 and xCT, the catalytic subunit of the cystine-glutamate exchanger, following cocaine self-administration and 3 weeks of extinction training. We also examined the affect of ceftriaxone (previously shown to increase GLT-1) and N-acetylcysteine treatment on the expression of GLT-1 and xCT. Ceftriaxone was also tested for the capacity to inhibit cue- and cocaine-induced relapse. RESULTS:Cocaine self-administration reduced glutamate uptake and the expression of both GLT-1 and xCT. Ceftriaxone restored GLT-1 and xCT levels and prevented cue- and cocaine-induced reinstatement of drug seeking. N-acetylcysteine also restored GLT-1 and xCT levels. CONCLUSIONS:These results indicate that glutamate transport and cystine-glutamate exchange may be coregulated and provide further evidence that targeting glutamate homeostasis is a potential method for treating cocaine relapse.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Knackstedt LA,Melendez RI,Kalivas PWdoi
10.1016/j.biopsych.2009.07.018subject
Has Abstractpub_date
2010-01-01 00:00:00pages
81-4issue
1eissn
0006-3223issn
1873-2402pii
S0006-3223(09)00892-0journal_volume
67pub_type
杂志文章abstract::Using computed tomography, lateral ventricular size was determined in 45 schizophrenic and 22 affective disorder patients, and was found in both patient groups to be greater than that of 62 similarly aged headache controls. While drug-free, the 15 schizophrenics with ventricles 1 standard deviation greater than the ag...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Biological psychiatry
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1016/0006-3223(91)90195-r
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:10.1016/0006-3223(93)90321-4
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(98)00319-9
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
doi:10.1016/j.biopsych.2013.02.010
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pub_type: 杂志文章
doi:10.1016/j.biopsych.2007.05.007
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2001-11-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.biopsych.2006.07.032
更新日期:2007-06-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0006-3223(00)01101-x
更新日期:2001-02-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2005.04.014
更新日期:2005-08-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.11.040
更新日期:2005-02-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2016-08-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.09.028
更新日期:2010-02-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2004.06.031
更新日期:2004-10-01 00:00:00
abstract:BACKGROUND:Clinically and biologically, autism spectrum disorder (ASD) is heterogeneous. Unusual patterns of visual preference as indexed by eye tracking are hallmarks; however, whether they can be used to define an early biomarker of ASD as a whole or leveraged to define a subtype is unclear. To begin to examine this ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2015.03.032
更新日期:2016-04-15 00:00:00