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

KS Hsu, CC Huang, MT Su and JJ Tsai

Department of Pharmacology and Neurology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, Republic of China.

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 microM) 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, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D- aspartate, was not affected by L-deprenyl (1 microM) pretreatment. In addition, L-deprenyl (1 microM) 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 microM) on the EPSP amplitude was specifically antagonized by sulpiride (0.01-0.1 microM), a selective dopamine D2 receptor antagonist. However, the dopamine D1 receptor antagonist, SKF- 83566 (1-10 microM), 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 microM) also reversibly suppressed the epileptiform activity evoked by picrotoxin.

Volume 279, Issue 2, pp. 740-747, 11/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1996 by the American Society for Pharmacology and Experimental Therapeutics.