کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278164 | 1295796 | 2008 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Blunted cystine-glutamate antiporter function in the nucleus accumbens promotes cocaine-induced drug seeking
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine-glutamate exchange via system xcâ, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xcâ. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xcâ. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0-60 mg/kg, i.p.) in the presence or absence of the system xcâ inhibitor (S)-4-carboxyphenylglycine (CPG; 0.5 μM; infused into the nucleus accumbens). N-acetylcysteine attenuated cocaine-primed reinstatement, and this effect was reversed by co-administration of CPG. Secondly, we examined whether reduced system xcâ activity is necessary for cocaine-primed reinstatement. To do this, we administered N-acetylcysteine (0 or 90 mg/kg, i.p.) prior to 12 daily self-administration sessions (1 mg/kg/200 μl, i.v.; 6 h/day) since this procedure has previously been shown to prevent reduced activity of system xcâ. On the reinstatement test day, we then acutely impaired system xcâ in some of the rats by infusing CPG (0.5 μM) into the nucleus accumbens. Rats that had received N-acetylcysteine prior to daily self-administration sessions exhibited diminished cocaine-primed reinstatement; this effect was reversed by infusing the cystine-glutamate exchange inhibitor CPG into the nucleus accumbens. Collectively these data establish system xcâ in the nucleus accumbens as a key mechanism contributing to cocaine-primed reinstatement.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 155, Issue 2, 13 August 2008, Pages 530-537
Journal: Neuroscience - Volume 155, Issue 2, 13 August 2008, Pages 530-537
نویسندگان
K.S. Kau, A. Madayag, J.R. Mantsch, M.D. Grier, O. Abdulhameed, D.A. Baker,