Role of the N-methyl-D-aspartate-type receptors in the development and maintenance of hippocampal kindling in rats

Neurosci Lett. 1988 Apr 22;87(1-2):63-8. doi: 10.1016/0304-3940(88)90146-2.


The effect of intrahippocampal infusion of 70 nmol (1 microliter/2 min) D,L-2-amino-7-phosphonoheptanoic acid (APH), a selective antagonist of N-methyl-D-aspartate (NMDA)-type receptors, was studied on behavioral seizures and afterdischarge (AD) at different stages of hippocampal kindling in rats. After completion of kindling (3 consecutive stage 5 seizures) APH infusion at the site of stimulation (granule cells of dentate gyrus) 60 min before stimulus delivery (50 Hz, 2 ms monophasic rectangular wave pulses for 1 s, current intensity 60-200 microA) suppressed the behavioral convulsions and focal AD. Four stimulations were needed after drug injection to recover stage 5 seizures and AD. When similarly injected early in kindling (stage 1-2) APH had no effect on the AD duration but significantly increased (by 37% with respect to controls) the number of stimulations needed to reach the first stage 5 seizures. Thus, it appears that NMDA-type receptors at the site of stimulation become progressively involved during the development of kindling and mediate the behavioral convulsions and focal AD observed at stage 5.

MeSH terms

  • 2-Amino-5-phosphonovalerate* / analogs & derivatives*
  • Action Potentials / drug effects
  • Amino Acids / pharmacology*
  • Animals
  • Electric Stimulation
  • Hippocampus / drug effects
  • Hippocampus / physiopathology*
  • Kindling, Neurologic / drug effects*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Seizures / physiopathology


  • Amino Acids
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • 2-Amino-5-phosphonovalerate
  • 2-amino-7-phosphonoheptanoic acid