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PROTECTION AGAINST KAINATE NEUROTOXICITY BY PYRROLIDINE DITHIOCARBAMATE
Ist Teil von
Clinical and experimental pharmacology & physiology, 2004-05, Vol.31 (5-6), p.320-326
Ort / Verlag
Oxford, UK: Blackwell Science Pty
Erscheinungsjahr
2004
Quelle
MEDLINE
Beschreibungen/Notizen
Summary
1. The effect of pyrrolidine dithiocarbamate (PDTC) on kainate (KA)‐induced neurotoxicity was examined in Sprague‐Dawley rats.
2. At 10 mg/kg, i.p., KA produced seizures accompanied by neuronal loss in the hippocampus and increased levels of malondialdehyde (MDA) and protein carbonyl.
3. Pretreatment with PDTC (100 or 200 mg/kg, p.o., every 12 h ×5) blocked KA‐induced neurotoxicities (seizures, increases in MDA and protein carbonyl and neuronal losses) in a dose‐dependent manner. These effects were counteracted by the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (25 or 50 µg/kg, i.p.), but not by the A2A receptor antagonist 1,3,7‐trimethyl‐8‐(3‐chlorostyryl)xanthine (0.5 or 1 mg/kg, i.p.) or the A2B receptor antagonist alloxazine (1.5 or 3.0 mg/kg, i.p.).
4. Our results suggest that the anticonvulsant and neuroprotective effects of PDTC are mediated, at least in part, via adenosine A1 receptor stimulation.