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 microM) 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 microM, L-deprenyl did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons. The limitation of RF by L-deprenyl (20 microM) was accompanied by the reduction of the maximal rate of rise (Vmax) of the action potentials in a non-voltage-dependent manner. In 80% of recorded cells, application of L-deprenyl (20 microM) 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-benzaz epine (SKF-83566, 5 microM), a selective D1 dopaminergic receptor antagonist. However, the D2 dopaminergic receptor antagonist, sulpiride (5 microM), 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 D1 dopaminergic receptor is involved in L-deprenyl's action.
Huang
C C
CC
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan.
Tsai
J J
JJ
Hsu
K S
KS
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology*
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D017447:Receptors, Dopamine D1; D012642:Selegiline; C051448:4-phenylpyridine; D010293:Pargyline; D004298:Dopamine