Glutamate transporter GLT-1 mediates N-acetylcysteine inhibition of cocaine reinstatement.
Glutamate transporter GLT-1 mediates N-acetylcysteine inhibition of cocaine reinstatement.
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DOI：
10.1111/adb.12127
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发表时间：
2015-03
影响因子：
3.4
通讯作者：
Kalivas PW
中科院分区：
文献类型：
--
作者：
Reissner KJ;Gipson CD;Tran PK;Knackstedt LA;Scofield MD;Kalivas PW
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. Rats were pre-treated in the nucleus accumbens with vivo-morpholino anti-sense oligomers targeting either GLT-1 or xCT (catalytic subunit of the cystine-glutamate exchanger) overlapping with daily NAC administration during extinction (100 mg/kg, i.p. for the last 5 days). Rats then underwent cue-induced reinstatement of active lever pressing in the absence of NAC, to determine if preventing NAC-induced restoration of one or the other protein was sufficient to block the capacity of chronic NAC to inhibit reinstatement. The vivo-morpholino suppression of xCT reduced cystine-glutamate exchange but did not affect NAC-induced reduction of reinstated cocaine seeking. In contrast, suppressing NAC-induced restoration of GLT-1 not only prevented NAC from inhibiting reinstatement, but augmented the capacity of cues to reinstate cocaine seeking. We hypothesized that the increased reinstatement after inhibiting NAC induction of GLT-1 resulted from increased extracellular glutamate, and show that augmented reinstatement is prevented by blocking mGluR5. Restoring GLT-1, not cystine-glutamate exchange, is a key mechanism whereby daily NAC reduces cue-induced cocaine reinstatement.
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影响因子：
25
作者：
Moussawi, Khaled;Pacchioni, Alejandra;Moran, Megan;Olive, M. Foster;Gass, Justin T.;Lavin, Antonieta;Kalivas, Peter W.
通讯作者：
Kalivas, Peter W.
DOI：
10.1124/jpet.109.151357
发表时间：
2009-06-01
影响因子：
3.5
作者：
Martin-Fardon, R.;Baptista, M. A. S.;Weiss, F.
通讯作者：
Weiss, F.
影响因子：
5.9
作者：
FLANAGAN, RJ;MEREDITH, TJ
通讯作者：
MEREDITH, TJ
DOI：
10.1016/j.pbb.2011.04.015
发表时间：
2012-02
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Olive MF;Cleva RM;Kalivas PW;Malcolm RJ
通讯作者：
Malcolm RJ
DOI：
10.1523/jneurosci.3452-10.2011
发表时间：
2011-04-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Reissner KJ;Uys JD;Schwacke JH;Comte-Walters S;Rutherford-Bethard JL;Dunn TE;Blumer JB;Schey KL;Kalivas PW
通讯作者：
Kalivas PW