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 Mg(2+)-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 Mg(2+)-free artificial CSF. These results suggest that tricyclic antidepressants block the induction of long-term potentiation by inhibitory actions on NMDA receptors.
Watanabe
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Abe
K
K
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013569:Synapses / Q000187:drug effects*; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D016194:Receptors, N-Methyl-D-Aspartate