Effects of standardized extracts of St. John's wort on the single-unit activity of serotonergic dorsal raphe neurons in awake cats: Comparisons with fluoxetine and sertraline

Casimir A. Fornal, Christine W. Metzler, Christian Mirescu, Susan K. Stein, Barry L. Jacobs

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

St. John's wort is widely used as an herbal remedy for depression. Although its mechanism of action remains unknown, some evidence suggests that St. John's wort might act via brain serotonin (e.g., as a serotonin reuptake inhibitor). To determine whether St. John's wort affects the central serotonergic system, we monitored the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of awake cats following systemic administration of two clinical preparations of St. John's wort, Jarsin® 300 (15-600 mg/kg, p.o.) and Hyperforat® (0.5-4.0 ml, i.v.). Both preparations were found to have no effect on neuronal activity. This contrasts sharply with the action of fluoxetine and sertraline (2 mg/kg, p.o.), two selective serotonin reuptake inhibitors (SSRIs), which markedly depressed neuronal activity by increasing the synaptic availability of serotonin at inhibitory somatodendritic 5-HT1A autoreceptors. The failure of St. John's wort to depress neuronal activity cannot be attributed to an impairment of the 5-HT1A autoreceptor mechanism, since pretreatment with Jarsin® 300 (300 mg/kg, p.o.) did not alter the responsiveness of serotonergic neurons to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (10 μg/kg, i.v.). Overall, these findings indicate that the mode of action of St. John's wort is different from that of conventional antidepressant drugs, which elevate brain serotonin and evoke negative feedback control of serotonergic neurons.

Original languageEnglish (US)
Pages (from-to)858-870
Number of pages13
JournalNeuropsychopharmacology
Volume25
Issue number6
DOIs
StatePublished - Dec 1 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Keywords

  • 5-hydroxytryptamine (serotonin)
  • Antidepressants
  • Dorsal raphe nucleus
  • Electrophysiology
  • Hypericum perforatum
  • LI 160
  • Selective serotonin reuptake inhibitors

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