title: L-deprenyl (selegiline) decreases excitatory synaptic transmission in the rat hippocampus via a dopaminergic mechanism.
abstract: 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.
authors.affiliation: Department of Pharmacology and Neurology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, Republic of China.
authors.forename: K S
authors.initials: KS
authors.lastname: Hsu
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: M T
authors.initials: MT
authors.lastname: Su
authors.forename: J J
authors.initials: JJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D004298:Dopamine; D005973:Glutamine; D008996:Monoamine Oxidase Inhibitors; D016202:N-Methylaspartate; D010293:Pargyline; D010852:Picrotoxin; D011725:Pyridines; D017448:Receptors, Dopamine D2; D012642:Selegiline; C051448:4-phenylpyridine