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• W1966793038 abstract "Extracts of the medicinal plant St. John's wort (Hypericum perforatum) are widely used for the treatment of mild to moderate depression. Hyperforin, a constituent of St. John's wort, is known to inhibit the sodium-dependent uptake of catecholamines and amino acids into synaptic nerve endings, probably by interference with mechanisms controlling the synaptic sodium concentration. Because de novo synthesis of acetylcholine (ACh) is dependent on sodium-dependent high-affinity choline uptake, we studied the effect of hyperforin on choline (Ch) uptake in vitro and on striatal ACh release in vivo using microdialysis. In rat brain synaptosomes, hyperforin inhibited high-affinity choline uptake with an IC(50) of 8.5 microM, whereas low-affinity uptake was not affected. Local infusion of hyperforin (100 microM) via the dialysis probe caused a delayed reduction of ACh release and a concomitant increase of Ch levels. Infusion of a lower concentration of hyperforin (10 microM), however, increased striatal ACh release and lowered Ch levels. Systemic administration of hyperforin (1-10 mg/kg i.p.) led to therapeutic plasma levels of hyperforin and caused a significant elevation of striatal ACh release. Behavioral testing revealed a reduction of locomotor activity in mice treated with high-dose (10 mg/kg) hyperforin. We conclude that low doses of hyperforin stimulate striatal ACh release by an unknown mechanism, whereas high doses inhibit synaptic choline uptake and ACh release. The results are discussed with respect to the therapeutic use of St. John's wort in patients with neurodegenerative disorders." @default.
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• W1966793038 date "2002-05-01" @default.
• W1966793038 modified "2023-10-10" @default.
• W1966793038 title "Dual Modulation of Striatal Acetylcholine Release by Hyperforin, a Constituent of St. John's Wort" @default.
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• W1966793038 doi "https://doi.org/10.1124/jpet.301.2.714" @default.
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