NMDA-induced seizures in developing rats cause long-term learning impairment and increased seizure susceptibility. 
N-methyl-D-aspartate (NMDA) receptors play a prominent role in the pathogenesis of epilepsy, yet few studies have used NMDA as a convulsant in whole animals.  In developing rats, systemic NMDA induces seizures with a unique seizure phenotype ("emprosthotonic" or hyperflexion seizures) and electrographic pattern (electrodecrement).  These features are not seen in kainic acid-induced seizures, suggesting that seizures activated by NMDA might cause different long-term consequences.  Therefore, we investigated the effects of NMDA seizures during development on cognitive function and susceptibility to seizures in adulthood.  Rat pups (P12-20) were injected with saline (n=36) or NMDA (n=64) at convulsant doses (15-30mg/kg, i.p.).  After NMDA injection, a characteristic sequence of seizure activity was seen: initial behavioral arrest, followed by hyperactivity, agitation, and then emprosthotonus and generalized tonic-clonic seizures.  Seizures were terminated 30min later by ketamine (50mg/kg, i.p.).  On P85, rats underwent behavioral testing in the water maze.  Rats that had experienced NMDA seizures as pups took significantly longer to learn the platform location over 5 days of testing, compared to controls.  On P90, rats were injected with pentylenetetrazol (PTZ, 50mg/kg, i.p.)  to assess their susceptibility to generalized seizures.  NMDA-treated rats had decreased latency and increased duration of class V PTZ seizures.  Cresyl violet-stained sections of cortex and hippocampus had no obvious cell loss or gliosis.  In summary, NMDA causes a unique seizure phenotype in the developing brain, with subsequent deficits in spatial learning and an increased susceptibility to PTZ seizures in adulthood.  This study provides additional evidence for long-term alterations of neuronal excitability and cognitive capacity associated with seizures during development.