TRICYCLIC ANTIDEPRESSANTS BLOCK NMDA RECEPTOR-MEDIATED SYNAPTIC RESPONSES AND INDUCTION OF LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES

The effects of tricyclic antidepressants (imipramine, desipramine and amitriptyline) on the NMDA receptor-mediated synaptic responses and the induction of long-term potentiation were investigated in the CA1 region and the dentate gyrus of rat hippocampal slices. Both in the CA1 region and in the dentate gyrus, all three antidepressants (3 x 10(-5)M) did not affect the evoked potential in normal artificial cerebrospinal fluid (CSF) but inhibited the NMDA receptor-mediated epileptiform responses in Mg2+-free artificial CSF. Furthermore, all three agents blocked the induction of long-term potentiation in a concentration-dependent manner, both in the CA1 region and in the dentate gyrus. The concentrations which were effective in blocking the induction of long-term potentiation were consistent with those in inhibiting the NMDA receptor-mediated synaptic responses in Mg2+-free artificial CSF. These results suggest that tricyclic antidepressants block the induction of long-term potentiation by inhibitory actions on NMDA receptors.