L-deprenyl (selegiline) decreases excitatory synaptic transmission in the rat hippocampus via a dopaminergic mechanism

Kuei Sen Hsu, Chiung Chun Huang, Mei Tsu Su, Jing Jane Tsai

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8 Citations (Scopus)


The effect of L-deprenyl (selegiline) on the excitatory synaptic transmission was characterized in the CA1 neurons of rat hippocampal slices by using a intracellular recording technique. Superfusion of L-deprenyl (0.1- 10 μM) reversibly decreased the EPSP, which was evoked by orthodromic stimulation of the Schaffer collateral-commissural afferent pathway in a concentration-dependent manner. The sensitivity of postsynaptic neurons to the glutamate receptor agonists, α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid or N-methyl-D-aspartate, was not affected by L-deprenyl (1 μM) pretreatment. In addition, L-deprenyl (1 αM) clearly increased the magnitude of paired-pulse facilitation regardless of the interstimulus intervals of 20 to 300 msec used. The ability of L-deprenyl to decrease the EPSP amplitude was not observed in the dopamine-depleted rats. Pargyline and 4-phenylpyridine, the monoamine oxidase type B inhibitors, mimicked the depressant effect of L-deprenyl on the EPSP. Moreover, the reduction of L- deprenyl (1 μM) on the EPSP amplitude was specifically antagonized by sulpiride (0.01-0.1 μM), a selective dopamine D2 receptor antagonist. However, the dopamine D1 receptor antagonist, SKF-83566 (1-10 μM), did not significantly affect L-deprenyl's action. These results indicate that the monoamine oxidase type B inhibitory ability leading to an increase of the dopaminergic tonus in the hippocampus is involved in the L-deprenyl-induced depression of excitatory synaptic transmission in the CA1 region of the rat hippocampus. Moreover, application of L-deprenyl (1 and 10 μM) also reversibly suppressed the epileptiform activity evoked by picrotoxin.

Original languageEnglish
Pages (from-to)740-747
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - 1996 Nov

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology


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