EFFECTS OF ANTIDEPRESSANTS ON THE GLUTAMATERGIC SYSTEM IN MOUSE-BRAIN

Several antidepressants and neuroleptics inhibited concentration-dependently the binding activity of [H-3]MK-801, an open channel blocker for N-methyl-D-aspartate (NMDA) receptor/channel, in mouse brain membranes. This inhibitory effect showed order potency: desipramine (DMI) > nomifensine > amitriptyline > imipramine > maprotiline > chlorpromazine > zotepine > amoxapine > clozapine > mianserin > viloxazine > zimelidine. The inhibitory manner of DMI for [H-3]MK-801 binding was similar to that of phencyclidine or Zn2+. The repeated administration of DMI (20 mg/kg i.p.; 3 weeks) induced decrease in glutamic acid, glycine and glutamine content in the hippocampus and increase in K(D) and B(max) of [H-3]MK-801 binding in the cerebral cortex, as was also noted for the 3-week administration of 20 mg/kg ketamine. These results clearly demonstrate antidepressants affect the glutamatergic system in the CNS and/or the effects may possibly be involved in blockade of NMDA receptor channel directly.