[Increase of 3H-GABA release from rat cultured cortex neurons after chronic exposure to MK801]

Excitatory amino acids are involved in acute and chronic neurodegenerative diseases. Little is known about the potential consequences of chronic blockade of NMDA receptors (one subtype of excitatory amino acid receptors). Receptor function measured as 3H-GABA release in culture media after pretreatment with MK801 was studied in rat cortical neurons in primary cultures. Cultured neurons were exposed to 1 mumol.L-1 MK801 for 4 days since the 14th day. Glutamate (1 mmol.L-1) evoked 3H-GABA release was shown to be significantly increased (control 0.2174/1000 +/- 1.40/1000; MK801 treatment 0.763% +/- 0.192%). KCl 40 mmol.L-1 stimulation showed no such effect. This result suggests that the NMDA receptor function of releasing neurotransmitters changed after chronic treatment with noncompetitive antagonists.