L-DEPRENYL (SELEGILINE) DECREASES EXCITATORY SYNAPTIC TRANSMISSION INTHE RAT HIPPOCAMPUS VIA A DOPAMINERGIC MECHANISM

The effect of L-deprenyl (selegiline) on the excitatory synaptic trans mission was characterized in the CA1 neurons of rat hippocampal slices by using a intracellular recording technique. Superfusion of L-depren yl (0.1-10 mu M) reversibly decreased the EPSP, which was evoked by or thodromic stimulation of the Schaffer collateral-commissural afferent pathway in a concentration-dependent manner. The sensitivity of postsy naptic neurons to the glutamate receptor agonists, lpha-amino-3-hydrox y-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate, was not affected by L-deprenyl (1 mu M) pretreatment. In addition, L-deprenyl (1 mu M) 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 mon oamine oxidase type B inhibitors, mimicked the depressant effect of L- deprenyl on the EPSP. Moreover, the reduction of L-deprenyl (1 mu M) o n the EPSP amplitude was specifically antagonized by sulpiride (0.01-0 .1 mu M), a selective dopamine D-2 receptor antagonist. However, the d opamine D-1 receptor antagonist, SKF-83566 (1-10 mu M), did not signif icantly affect L-deprenyl's action. These results indicate that the mo noamine oxidase type B inhibitory ability leading to an increase of th e dopaminergic tonus in the hippocampus is involved in the L-deprenyl- induced depression of excitatory synaptic transmission in the CA1 regi on of the rat hippocampus. Moreover, application of L-deprenyl (1 and 10 mu M) also reversibly suppressed the epileptiform activity evoked b y picrotoxin.