کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9012797 | 1125017 | 2005 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
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چکیده انگلیسی
Previous studies have shown that chronic opiate treatment decreases mu opioid-stimulated [35S]GTPγS binding in specific brain regions. To extend these findings, the present study investigated DAMGO-stimulated [35S]GTPγS binding in membrane homogenates and coronal sections from rats non-contingently administered heroin. Rats were administered saline or increasing doses of heroin i.v. hourly up to 288 mg/kg/day over 40 days. In brain sections, chronic heroin administration decreased DAMGO-stimulated [35S]GTPγS binding in medial thalamus and amygdala, with no effect in cingulate cortex or nucleus accumbens. Chronic heroin administration also reduced [35S]GTPγS binding stimulated by the principal metabolite of heroin, 6-monoacetylmorphine. In contrast, no significant changes in mu opioid receptor binding were observed in amygdala or thalamus using [3H]DAMGO autoradiography. In membranes from amygdala and thalamus, chronic heroin treatment decreased the maximal effect of DAMGO in stimulating [35S]GTPγS binding, with no effect on DAMGO potency. GTPγS saturation analysis showed that chronic heroin treatment decreased the Bmax, and increased the KD, of DAMGO-stimulated [35S]GTPγS binding. These data suggest potential mechanisms by which chronic agonist treatment produces opioid receptor/G-protein desensitization in brain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 77, Issue 10, 22 July 2005, Pages 1140-1154
Journal: Life Sciences - Volume 77, Issue 10, 22 July 2005, Pages 1140-1154
نویسندگان
Catherine E. Maher, Thomas J. Martin, Steven R. Childers,