L-deprenyl (selegiline) limits the repetitive firing of action potentials in rat hippocampal CA1 neurons via a dopaminergic mechanism

The effects of L-deprenyl (selegiline), a highly selective monoamine oxidase type B (MAO-B) inhibitor, on cell excitability of rat hippocampal CA1 neurons were examined in slice preparations using intracellular recording techniques. Superfusion of L-deprenyl (10 and 20 mu M) reversibly limited the repetitive firing (RF) of action potentials elicited by injection of depolarizing current pulses (100 ms) into the pyramidal cells. At a concentration of 1-50 mu M, L-deprenyl did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons. The limitation of RF by L-deprenyl (20 mu M) was accompanied by the reduction of the maximal rate of rise ((V) over dot(max)) of the action potentials in a non-voltage-dependent manner. In 80% of recorded cells, application of L-deprenyl (20 mu M) produced an increase in the amplitude and duration of afterhyperpolarization (AHP). The limitation of L-deprenyl on RF was mimicked by other MAO-B inhibitors, pargyline and 4-phenylpyridine. In addition, the ability of L-deprenyl to limit RF was not observed in the hippocampal CA1 neurons taken from dopamine (DA)-depleted rats. Moreover, we also observed that the L-deprenyl-induced limitation of RF was specifically antagonized by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF-83566, 5 mu M), a selective D-1 dopaminergic receptor antagonist. However, the D-2 dopaminergic receptor antagonist, sulpiride (5 mu M), had no effect on L-deprenyl's action. These results indicate that the MAO-B inhibitory ability leading to an increase of the dopaminergic tone in the hippocampus is involved, at least in part, in the L-deprenyl-induced reduction of neuronal excitability in the CA1 region of rat hippocampus and that the D-1 dopaminergic receptor is involved in L-deprenyl's action. (C) 1997 Elsevier Science B.V.