Abstract
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 1 receptor antagonist 8-cyclopentyl-1,3-dimetliylxanthine (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 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 A1 receptor stimulation.
Original language | English |
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Pages (from-to) | 320-326 |
Number of pages | 7 |
Journal | Clinical and Experimental Pharmacology and Physiology |
Volume | 31 |
Issue number | 5-6 |
DOIs | |
Publication status | Published - 2004 May |
Externally published | Yes |
Keywords
- Adenosine A receptor
- Anti-oxidant
- Anticonvulsant effects
- Hippocampus
- Kainic acid
- Malondialdehyde
- Neuroprotective effects
- Protein carbonyl
- Pyrrolidine dithiocarbamate
ASJC Scopus subject areas
- Physiology
- Pharmacology
- Physiology (medical)