Stimulation of hippocampal acetylcholine release by hyperforin, a constituent of St. John's Wort.
Extracts of the medicinal plant St. John's Wort (Hypericum perforatum) are widely used in the therapy of affective disorders and have been reported to exert antidepressant, anxiolytic, and cognitive effects in experimental and clinical studies. We here report that hyperforin, the major active constituent of the extract, increases the release of acetylcholine from rat hippocampus in vivo as determined by microdialysis. Hippocampal acetylcholine levels were increased by 50-100% following the systemic administration of pure hyperforin at doses of 1 and 10 mg/kg. The effect was almost completely suppressed by local perfusion with calcium-free buffer or with tetrodotoxin (1 microM). We conclude that hyperforin releases hippocampal acetylcholine by an indirect mechanism of action which is calcium-dependent and requires intact neuronal communication and cell firing. Our findings suggest therapeutic efficacy of St. John's Wort extracts in central cholinergic dysfunction.
Kiewert
Cornelia
C
Department of Pharmaceutical Sciences, Texas Tech School of Pharmacy, 1300 Coulter Drive, Amarillo 79106, USA.
Buchholzer
Marie-Luise
ML
Hartmann
Joachim
J
Chatterjee
Shyam Sunder
SS
Klein
Jochen
J
D000109:Acetylcholine / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020902:Hypericum / Q000737:chemistry; D017551:Microdialysis; D010696:Phloroglucinol / Q000031:analogs & derivatives; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D010936:Plant Extracts; D013729:Terpenes; D013779:Tetrodotoxin; D010696:Phloroglucinol; D000109:Acetylcholine; C001654:hyperforin