Traxoprodil decreases pentylenetetrazol-induced seizures

Polyamines, including spermidine, facilitate seizures by positively modulating N-methyl-D-aspartate receptors (NMDAr). Although NMDAr antagonists decrease seizures, it remains to be determined whether traxoprodil, a selective antagonist at the NR2B subunit of the NMDAr, decreases seizures and whether spermidine facilitates pentylenetetrazol (PTZ)-induced seizures. Adult male Wistar rats were injected in the lateral ventricle with 0.9% NaCl (1 mu l, i.c.v.), spermidine (0.02, 0.2 or 2 nmol/site, i.c.v.) or traxoprodil (0.2, 2 or 20 nmol, i.c.v.) and with PTZ (35 or 70 mg/kg, i.p.). The effect of orally administered traxoprodil (60 mg/kg, p.o.) on seizures was also investigated. Latencies to clonic and generalized seizures, as well the total time spent in seizures were recorded by behavioral and electrographic methods (EEG). Spermidine (2 nmol/site; i.c.v.) facilitated the seizures induced by a sub-threshold dose of PTZ (35 mg/kg; i.p.), but did not alter seizure activity induced by a convulsant dose of PTZ (70 mg/kg; i.p.). Traxoprodil (20 nmol i.c.v.) increased the latency to generalized tonic clonic seizures induced by PTZ (70 mg/kg; i.p.). Traxoprodil (60 mg/kg, p.o.) increased the latency to clonic and generalized seizures, and decreased the total time spent in seizures. These results support the role for the NR2B subunit in PTZ-induced seizures. (C) 2012 Elsevier B.V. All rights reserved.