• carbamazepine;
  • glutamate;
  • microdialysis electrode;
  • spreading depression;
  • zonisamide
  • 1
    Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed.
  • 2
    Basal glutamate levels were below detection limits (∼0.1 μm). An increase in extracellular KCl (from 2.7 to 50 and 100 mm) increased extracellular hippocampal glutamate levels to 9.2±1.4 and 20.0±2.6 μm, respectively, calculated from the area under curve (AUC) for 60 min.
  • 3
    This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises.
  • 4
    An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mm KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2±1.4 to 12.4±2.1 and 5.8±0.9 μm.
  • 5
    Perfusion with 100 μm CBZ or 1 mm ZNS inhibited both the 50 mm KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2±1.4 to 5.5±1.1 and to 5.8±1.3 μm, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release.
  • 6
    These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.

British Journal of Pharmacology (1998) 124, 1277–1285; doi:10.1038/sj.bjp.0701941