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

Abstract

St. John's wort, p.o.) and 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.) 8-hydroxy-2-(di-n-propylamino)tetralin (10 g/kg, i.v.). Overall, these -hydroxytryptamine (serotonin); ElectrophysiologyThe medicinal plant Hypericum perforatum L., commonly known as St. John's wort, appears to be an effective antidepressant with few side effects (Hippius 1998;Wheatley 1998;Vitiello 1999). In Germany, where extracts of the plant are licensed as a medication, St. John's wort or hypericum is used more extensively than et al. 1996). Since the publication of that influential report, several other systematic reviews (and one metaanalysis) have appeared which further support the antidepressant efficacy of hypericum (Josey and Tackett 1999;Kim et al. 1999;Stevinson and Ernst 1999;Gaster and Holroyd 2000). Furthermore, in comparison with other antidepressants, St. John's wort is well tolerated and has a low side effect profile (Linde et al. 1996;Ernst et al. 1998 Despite its widespread use, the active constituents and mechanism of antidepressant action of St. John's wort remain largely unknown (Bennett et al. 1998;Nathan 1999). A number of studies have shown that crude hypericum preparations and some of the constituents can inhibit monoamine oxidase (MAO) activity in vitro (Demisch et al. 1989;Thiede and Walper 1994;Cott 1997;. However, the clinical relevance of this pharmacological effect is questionable, since it occurs only at high concentrations and has not been observed in vivo (Bladt and Wagner 1994;Yu 2000). More recent studies have focused on the capacity of St. John's wort to inhibit the uptake of brain monoamines, particularly serotonin Neary and Bu 1999). Perovic and Müller (1995) were the first to report that a crude hypericum extract inhibited the uptake of serotonin in rat cortical synaptosomes at relatively low concentrations and conclude that the antidepressant activity of St. John's wort is due to this action. Hypericum has also been shown to inhibit the synaptosomal uptake of dopamine and norepinephrine, at concentrations similar to those found to inhibit the uptake of serotonin . In subsequent studies, the chemical substance hyperforin was identified as one of the major uptake-inhibiting components of St. John's wort Chatterjee et al. 1998;Singer et al. 1999). The content of this substance has recently been associated with the clinical antidepressant action of St. John's wort (Laakmann et al. 1998), suggesting that hyperforin is at least partially responsible for the antidepressant properties of the herb. Other evidence suggest that hypericum extracts may enhance the release of serotonin from presynaptic stores (Gobbi et al. 1999). Neurochemical studies have shown that St. John's wort increases serotonin metabolism and/or turnover in various brain regions (Calapai et al. 1999;Yu 2000). Finally, it has been hypothesized that the clinical efficacy of St. John's wort may result from a combinati...

Antidepressant Effect ofTetragonia tetragonoides (Pall.) KuntzeExtract on Serotonin Turnover

“…Herbal extracts have recently been reported as complementary therapies for antidepressant purposes, and this type of treatment is expected to prevent onset of mood disorders and regulate serotonin reuptake activity [35, 36]. However, these alternative remedies are limited in the treatment of severe depression [9, 37]. In the present study, we examined TPH-1 and TPH-2 mRNA expression levels in RBL-2H3 cells after treatment with 0, 50, and 100 μ g/mL of TTK.…”

The antidepressant mechanism of Hypericum perforatum

“…Another study (Fornal et al, 2001) found no effect of SJW extracts on the firing rate of 5-HT neurons in the cat dorsal raphe, which is inhibited by compounds such as the 5-HT reuptake inhibitors, that increase the synaptic availability of 5-HT. At variance with these results, a ''push-pull superfusion'' study in the rat locus coeruleus showed that systemic hyperforin induced a lasting (>5 h) and marked (100-200%) increase in the extracellular concentrations of 5-HT, but not 5-HIAA (Kaehler et al, 1999).…”

Role of serotonergic dorsal raphe neurons in hypercapnia-induced arousals

“…There are several possibilities for this discrepancy. One is that the stimulation rate used by Ito and colleagues may be outside the physiological firing range for DR neurons, which typically fire at ~3 Hz during quiet wake, but were stimulated at 20 Hz optogenetically 34 . Another possibility is that Ito et al used Tph-Chr2 mice that express channelrhodopsin in all serotonergic neurons.…”