Caffeine and an adenosine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life

J Neurochem. 2010 Jan;112(2):453-62. doi: 10.1111/j.1471-4159.2009.06465.x. Epub 2009 Oct 30.


Seizures early in life cause long-term behavioral modifications, namely long-term memory deficits in experimental animals. Since caffeine and adenosine A(2A) receptor (A(2A)R) antagonists prevent memory deficits in adult animals, we now investigated if they also prevented the long-term memory deficits caused by a convulsive period early in life. Administration of kainate (KA, 2 mg/kg) to 7-days-old (P7) rats caused a single period of self-extinguishable convulsions which lead to a poorer memory performance in the Y-maze only when rats were older than 90 days, without modification of locomotion or anxiety-like behavior in the elevated-plus maze. In accordance with the relationship between synaptotoxicity and memory dysfunction, the hippocampus of these adult rats treated with kainate at P7 displayed a lower density of synaptic proteins such as SNAP-25 and syntaxin (but not synaptophysin), as well as vesicular glutamate transporters type 1 (but not vesicular GABA transporters), with no changes in PSD-95, NMDA receptor subunits (NR1, NR2A, NR2B) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits (GluR1, GluR2) compared with controls. Caffeine (1 g/L) or the A(2A)R antagonist, KW6002 (3 mg/kg) applied in the drinking water from P21 onwards, prevented these memory deficits in P90 rats treated with KA at P7, as well as the accompanying synaptotoxicity. These results show that a single convulsive episode in early life causes a delayed memory deficit in adulthood accompanied by a glutamatergic synaptotoxicity that was prevented by caffeine or adenosine A(2A)R antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Caffeine / administration & dosage*
  • Disease Models, Animal
  • Disease Progression
  • Drug Administration Schedule
  • Glial Fibrillary Acidic Protein / metabolism
  • Kainic Acid
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / prevention & control*
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Purines / administration & dosage*
  • Pyrimidines / pharmacology
  • Qa-SNARE Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Seizures / chemically induced
  • Seizures / complications
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptophysin / metabolism
  • Synaptosomal-Associated Protein 25 / metabolism
  • Triazoles / pharmacology
  • Tritium / metabolism
  • Xanthines / metabolism


  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Adenosine A2 Receptor Antagonists
  • Glial Fibrillary Acidic Protein
  • Phosphodiesterase Inhibitors
  • Purines
  • Pyrimidines
  • Qa-SNARE Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Snap25 protein, rat
  • Synaptophysin
  • Synaptosomal-Associated Protein 25
  • Triazoles
  • Xanthines
  • Tritium
  • istradefylline
  • Caffeine
  • 1,3-dipropyl-8-cyclopentylxanthine
  • Kainic Acid