ACUTE EFFECTS OF ANTIDEPRESSANT DRUGS ON LONG-TERM POTENTIATION (LTP) IN RAT HIPPOCAMPAL SLICES

The actions of three clinically effective antidepressant drugs with different pharmacological profiles were investigated in the CA1 area of rat hippocampal slices. Imipramine and (+) or (-)-oxaprotiline had negligible effects on population spikes evoked by stratum radiatum stimulation, but reduced postsynaptic excitability in low Ca high Mg medium after an exposure of more than 15 min. Imipramine and (+)-oxaprotiline at 10-mu-mol/l enhanced long-term potentiation (LTP) when a lower stimulation strength was applied while (+)-oxaprotiline reduced LTP when a higher stimulus amplitude was used to evoke population spikes. (-)-oxaprotiline (levoprotiline) had a similar effect which was, however, not significant in either stimulation paradigm at the P < 0.05 level. Imipramine actions were also studied on epileptiform discharges in Mg2+-free medium: a facilitation-inhibition sequence with a slow time course was seen with 50-mu-mol/l but no effect with 10-mu-mol/l. An involvement of N-methyl-D-aspartate (NMDA)-receptors in acute actions of antidepressants is unlikely but long-term potentiation in the hippocampus is modulated by these drugs.