Protection against kainate neurotoxicity by pyrrolidine dithiocarbamate

초록

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 X5) 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 A, receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 mug/kg, i.p.), but not by the A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyrvl)xanthine (0.5 or 1 mg/kg, i.p.) or the A(2B) 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 A, receptor stimulation.

키워드