کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4330384 1614252 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Potentiation of N-methyl-d-aspartate receptor-mediated neuronal injury during methamphetamine withdrawal in vitro requires co-activation of IP3 receptors
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Potentiation of N-methyl-d-aspartate receptor-mediated neuronal injury during methamphetamine withdrawal in vitro requires co-activation of IP3 receptors
چکیده انگلیسی

Recent findings suggest that methamphetamine (METH) functions acutely to inhibit N-methyl-d-aspartate (NMDA) receptor function. Protracted withdrawal from METH exposure may increase the sensitivity of NMDA receptors to agonist exposure, promoting neuronal excitability. However, the relevance of METH effects on NMDA receptor activity with regard to neuronal viability has not been fully studied. The present studies examined the effects of protracted METH exposure (6 or 7 days; 1.0–100 μM) and withdrawal (1 or 7 days) on NMDA receptor-dependent neurotoxicity, determined with use of the non-vital fluorescent marker propidium iodide, in organotypic slice cultures of male and female rats. Prolonged exposure to METH (100 μM) produced only modest toxicity in the granule cell layer of the dentate gyrus. Withdrawal from METH exposure (1 or 7 days) did not produce overt neuronal injury in any region of slice cultures. Exposure to NMDA (5 μM) produced marked neurotoxicity in the CA1 pyramidal cell layer. Neither co-exposure to METH nor 1 day of METH withdrawal in combination with NMDA exposure altered NMDA-induced neurotoxicity. In contrast, protracted withdrawal from METH exposure (7 days) was associated with a marked (∼400%) increase in NMDA-induced neurotoxicity in CA1 region pyramidal cells. This potentiation of neurotoxicity was prevented by co-exposure to the selective NMDA receptor antagonist 5-2-amino-5-phoshonovaleric acid (20 μM) and was markedly attenuated by co-exposure of slices to xestospongin C (1 μM), an antagonist of IP3 receptors. The results of the present studies suggest that long-term METH withdrawal functionally sensitizes the NMDA receptor to agonist exposure and requires the co-activation of NMDA and IP3 receptors.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1187, 2 January 2008, Pages 67–73
نویسندگان
, , , , ,