کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2537317 1559179 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Stimulation of mitogen-activated protein kinase kinases (MEK1/2) by μ-, δ- and κ-opioid receptor agonists in the rat brain: Regulation by chronic morphine and opioid withdrawal
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Stimulation of mitogen-activated protein kinase kinases (MEK1/2) by μ-, δ- and κ-opioid receptor agonists in the rat brain: Regulation by chronic morphine and opioid withdrawal
چکیده انگلیسی

Opioid addiction modulates the extracellular signal-regulated kinase (ERK) leading to synaptic plasticity in the brain. ERK1/2 are stimulated by mitogen-activated protein kinase kinases (MEK1/2), but little is known about the regulation of MEK activity by opioid drugs. This study was designed to assess the acute effects of selective μ-, δ-, and κ-opioid receptor agonists, as well as those induced by chronic morphine and opioid withdrawal, on the content of phosphorylated MEK1/2 in the rat brain. Sufentanil (1–30 μg/kg, 30–120 min) induced dose- and time-dependent increases in MEK1/2 phosphorylation in the cerebral cortex and corpus striatum (30–177%) through a naloxone-sensitive mechanism. Morphine (100 mg/kg, 2 h) also augmented MEK1/2 phosphorylation in the both brain regions (50–70%). Similarly, the selective δ-opioid receptor agonist SNC-80 (10 mg/kg, 30 min) increased MEK1/2 activity in the cortex (60%) that was antagonized by naltrindole. In contrast, the selective κ-opioid receptor agonist (−)-U50488H (10 mg/kg, 30–120 min) did not modify significantly MEK1/2 phosphorylation in the cortex. Chronic morphine (10–100 mg/kg, 5 days) was not associated with alterations in the content of phosphorylated MEK1/2 in the brain (induction of tachyphylaxis to the acute effects). In morphine-dependent rats, however, naloxone (2 mg/kg)-precipitated withdrawal (2–6 h) induced robust increases in MEK1/2 phosphorylation in cortex (27–49%) and striatum (83–123%). Spontaneous opioid withdrawal (24 h) in morphine-dependent rats did not alter MEK1/2 activity in the brain. The findings may be relevant in the context of the pivotal role played by the MEK/ERK pathway in various long-lasting forms of synaptic plasticity associated with opioid addiction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 539, Issues 1–2, 6 June 2006, Pages 49–56
نویسندگان
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