کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2531951 | 1558954 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
mGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats
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کلمات کلیدی
PAMmGlu2/3Conditioned avoidance - اجتناب شرطیSchizophrenia - اسکیزوفرنی یا شیزوفرنیMED - باBINA - بایناMinimum effective dose - حداقل دوز موثرLocomotion - حرکتAntipsychotics - داروهای ضد روانپریشیAllosteric modulator - مدولاتور آلوده کنندهpositive allosteric modulator - مدولاتور آلوده کننده مثبتnegative allosteric modulator - منحنی آلوزیستریک منفیNAM - نام
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Inhibition of conditioned avoidance behavior in rats is generally considered predictive for antipsychotic activity in man. The present study investigated the mGlu2-mediated modulation of conditioned avoidance and compared mGlu2 agonists with available antipsychotics for their relative effects on conditioned avoidance behavior and locomotion. The mGlu2/3 orthosteric agonist 4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide (LY-404039) and mGlu2 positive allosteric modulator (PAM) 3-(cyclopropylmethyl)-7-(4-phenylpiperidin-1-yl)-8-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605) inhibited avoidance and blocked escape behavior. The mGlu2/3 negative allosteric modulators (NAMs) 7-(dimethylamino)-4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-2 H-1,5-benzodiazepin-2-one (JNJ-42112265) and 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-2H-1,5-benzodiazepin-2-one (RO-4491533) reversed the LY-404039-induced impairment of avoidance and escape. JNJ-42112265 also reversed the impairment of avoidance and escape induced by the mGlu2-specific PAM JNJ-42153605, suggesting that the effects on conditioned avoidance are specifically mGlu2-mediated. The mGlu2/3 antagonist (2-(2-carboxycyclopropyl)-3-(9H-xanthen-9-yl)-d-alanine (LY-341495; s.c.) reversed the LY-404039-induced escape impairment but failed to restore avoidance, suggesting interfering side effects. Like the tested antipsychotics, mGlu2/3 orthosteric and allosteric agonists inhibited avoidance behavior and locomotion at similar doses. Hence no clear-cut differences between mGlu2 modulators and currently available antipsychotics in the way they interfere with avoidance behavior in relation to inhibition of locomotion could be established.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 727, 15 March 2014, Pages 130-139
Journal: European Journal of Pharmacology - Volume 727, 15 March 2014, Pages 130-139
نویسندگان
Anton A.H.P. Megens, Herman M.R. Hendrickx, Koen A. Hens, Willem J.-P.E. Talloen, Hilde Lavreysen,