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The antidepressant tianeptine persistently modulates glutamate receptor currents of the hippocampal CA3 commissural associational synapse in chronically stressed rats
Author(s) -
Kole Maarten H. P.,
Swan Laura,
Fuchs Eberhard
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02136.x
Subject(s) - tianeptine , ampa receptor , nmda receptor , kainate receptor , excitatory postsynaptic potential , neuroscience , chemistry , glutamate receptor , long term depression , pharmacology , hippocampus , biology , receptor , antidepressant , inhibitory postsynaptic potential , biochemistry
Recent hypotheses on the action of antidepressants imply a modulation of excitatory amino acid transmission. Here, the effects of long‐term antidepressant application in rats with the drug tianeptine were examined at hippocampal CA3 commissural associational (c/a) glutamate receptor ion channels, employing the whole‐cell patch‐clamp technique. The drug's impact was tested by subjecting rats to daily restraint stress for three weeks in combination with tianeptine treatment (10 mg/kg/day). Whereas stress increased the deactivation time‐constant and amplitude of the N ‐methyl‐ d ‐aspartate (NMDA) receptor‐mediated excitatory postsynaptic currents (EPSCs), it did not affect the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainate receptor‐mediated EPSCs. Concomitant pharmacological treatment of stressed animals with tianeptine resulted in a normalized scaling of the amplitude ratio of NMDA receptor to AMPA/kainate receptor‐mediated currents and prevented the stress‐induced attenuation of NMDA‐EPSCs deactivation. Both paired‐pulse‐facilitation and frequency‐dependent plasticity remained unchanged. Both in control and stressed animals, however, tianeptine treatment strengthened the slope of the input‐output relation of EPSCs. The latter was mimicked by exposing hippocampal slices in vitro with 10 µ m tianeptine, which rapidly increased the amplitudes of NMDA‐ and AMPA/kainate EPSCs. The enhancement of EPSCs could be blocked by the intracellular presence of the kinase inhibitor staurosporine (1 µ m ), suggesting the involvement of a postsynaptic phosphorylation cascade rather then presynaptic release mechanisms at CA3 c/a synapses. These results indicate that tianeptine targets the phosphorylation‐state of glutamate receptors at the CA3 c/a synapse. This novel signal transduction mechanism for tianeptine may provide a mechanistic resolution for its neuroprotective properties and, moreover, a pharmacological trajectory for its memory enhancing and/or antidepressant activity.