Vázquez-López A, Sierra-Paredes G, Sierra-Marcuño G.
Anticonvulsant effect of the calcineurin inhibitor ascomycin on
seizures induced by picrotoxin microperfusion in the rat
hippocampus.
Pharmacol Biochem Behav. 2006 Jul;84(3):511-6. Epub 2006 Jul
26.
Neuroscience Division, Department of Biochemistry and
Molecular Biology, School of Medicine, University of Santiago,
San Francisco 1, 15782 Santiago de Compostela, Spain.
The potential in vivo anticonvulsant effect of calcineurin
(protein phosphatase 2B) inhibitor ascomycin against seizures
induced by intrahippocampal microdialysis of picrotoxin was
examined in the present study. After establishing individual
picrotoxin seizure thresholds, ascomycin was continually
microperfused into the rat hippocampus through microdialysis
probes at concentrations 10, 50 and 100 microM. No behavioral or
electroencephalographic effects were observed during
microperfusion of ascomycin alone. Low concentrations (10 microM)
of ascomycin did not prevent picrotoxin seizures, however, 50
and 100 microM ascomycin showed antiepileptic effect, completely
suppressing seizures in 41.7% and 75% of the animals studied
respectively. Mean seizure duration and mean number of seizures
were significantly reduced (P < 0.01) by microperfusion of 100
microM ascomycin. Calcineurin activity might be involved in the
biochemical changes leading to picrotoxin-induced epileptic
seizures. The present findings provide additional in vivo
evidence of the involvement of phosphorylation/dephosphorylation
mechanisms in the development of epileptic seizures, suggesting
that calcineurin modulation may be a possible strategy in the
search for new anticonvulsant drugs.
PMID: 16872668 |
