کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9425890 | 1295896 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Blunted response to cocaine in the Flinders hypercholinergic animal model of depression
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کلمات کلیدی
PBSrostral poleFR-1dpmFlinders resistant lineFRLFSL5HIAADOPACSSCmRNA3,4-dihydroxyphenylacetic acid - 3،4-دی هیدروکسی فنیل اسیدهای اسید5-hydroxyindole acetic acid - 5-hydroxyindole اسید استیکstandard saline citrate - استاندارد سدیم سیتراتself-administration - خود ادارهDopamine - دوپامینdisintegration per minute - فروپاشی در هر دقیقهLocomotor activity - فعالیت locomotorFlinders sensitive line - فلیندرز حساس خطPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریRat - موش صحراییfixed ratio 1 - نسبت ثابت 1nucleus accumbens core - هسته accumbens هستهnucleus accumbens shell - هسته accumbens پوستهhomovanillic acid - هومووانیلیک اسیدprodynorphin - پروین دینورفینHVA - چهhigh performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کارا
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The Flinders sensitive line (FSL) rat is a proposed genetic hypercholinergic animal model of human depression. Considering the strong comorbidity between depression and cocaine dependence we investigated the well-documented behavioral and molecular effects of cocaine in the FSL and their control Flinders resistant line (FRL) rats. First, we found no difference between the two lines to establish cocaine self-administration; both lines reached stable responding within 10 days of training at a fixed ratio-1 schedule of reinforcement (1.5 mg/kg/injection). However, the FSL rats exhibited reduced cocaine intake at a dose of 0.09 mg/kg/injection in a within-session dose-response curve (0.02, 0.09, 0.38, 1.5 mg/kg/injection). Second, we examined the effects of repeated cocaine administration on locomotor activity, dopamine overflow and striatal prodynorphin mRNA expression. We found the FSL rats to be low responders to novelty and to exhibit less locomotor activation after repeated cocaine administration (30 mg/kg, i.p., daily injections for 10 days) than their controls. Microdialysis sampling from the nucleus accumbens shell revealed no significant difference in the dopamine overflow between the rat lines, neither during baseline nor after cocaine stimulation. Postmortem analyses of striatal prodynorphin mRNA expression (using in situ hybridization histochemistry) revealed a differentiated response to the cocaine exposure. In contrast to control FRL rats, the FSL rats showed no typical cocaine-evoked elevation of prodynorphin mRNA levels in rostral subregions of the striatum whereas both strains expressed increased prodynorphin mRNA levels in the caudal striatum after cocaine administration. In conclusion, the FSL animal model of depression demonstrates marked blunting of the locomotor and dynorphin neuroadaptative responses to cocaine in accordance with its enhanced cholinergic sensitivity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 132, Issue 4, 2005, Pages 1159-1171
Journal: Neuroscience - Volume 132, Issue 4, 2005, Pages 1159-1171
نویسندگان
P. Fagergren, D.H. Overstreet, M. Goiny, Y.L. Hurd,